Complete Leukemias in 1 Shot | Hematology | A Comprehensive Guide by Dr. Priyanka Sachdev

Hello everyone, a very good evening to all of you. I hope I'm clearly visible and audible. So, I welcome you all for today's session. I am Dr. Priyanka Sajdev here, and today we all gathered here to study leukemias, right? So, let me see if everything is good to go. Everything is visible and audible. Just a second, let me see. Okay, I guess it's clearly visible. Okay. Hello.

So, today we are going to discuss leukemia. Do you find leukemia difficult? Yes or no? Do you find it difficult? Let me ask the same question after two hours. So, in the two hours, I'm going to make leukemia as a cakewalk for you, or fun for you. Let me ask the same question. Do you find leukemia difficult at the end of the session after two hours? Okay.

So, today in this session, we are going to compare the four leukemias, that is CML, AML, ALL, and CLL, in the most simplified possible manner in this world. So, you will find this session very interesting, very useful. Whatever exam you are targeting for, if you are a second prop student and you are targeting for your university exam in pathology, or you are in a final year and you are targeting your medicine exam, so in the hematology section, the leukemias will be useful for you. And if you are an intern or post-intern and you are targeting for any of the competitive exam like NET, PG, FMG, INIC, USMLE, PLAB, the session is going to be ultra useful for you. So, whatever section you take, leukemia is a very important topic, and students find it difficult. So, without wasting any further time, I guess I must start. So, let's start with leukemia. So, let me start. Let me share my screen with you. Give me a minute to share my screen with you. I guess you can see my screen. So, let's start the topic that is leukemia. Okay.

So, leukemia is basically, everyone knows it's a blood cancer. So, it is a disorder of blood. It's a disorder of blood. In the blood, basically, it's a disorder of WBC. So, if you want to understand every depth in leukemia, you must understand WBCs first. If you don't understand how the WBCs are formed in the bone marrow, what are the precursors of WBCs, you can't understand leukemia. So, let me start from the basic. I'm assuming that you don't know, you know nothing about leukemia. I'm starting from the scratch, and I will take you to the super basics of the leukemias. Let's start from the scratch. Okay. So, let's start it. Okay. Yes. So, let's start.

So, as I told you, leukemia is a disorder of WBC. So, let's first, in the five minutes, let's see how the WBCs are formed. Okay. What are WBCs? White blood cells. They are, they are, they are the leukocytes. How many types of WBCs are present in humans? There are five types of WBCs. There are five types. Basically, they are of two types: the granulocytes and agranulocytes. Granulocytes are the WBCs. They have granules present in their cytoplasm. That's why they are known as granulocytes. And agranulocytes are the WBCs. They don't have any granules in the cytoplasm. That's why they are known as A. A means absent. Absent. The granules are absent.

So, three of them are granulocytes. What are the three types of granulocytes? Neutrophil, Eosinophil, Basophil. Neutrophils have pink or purple granules in the cytoplasm. Appreciate it. Eosinophils have brick red color in the cytoplasm. Granules in the cytoplasm, brick red color. Appreciated. And basophils have dark blue or black color granules in the cytoplasm. But the common thing is that they all have granules in the cytoplasm. Got it? These are the granulocytes.

Coming on agranulocytes. They don't have granules in the cytoplasm, obviously. That's why they are known as agranulocytes. So, these are of two types: lymphocytes. We can see the nucleus and hardly any cytoplasm. You can see scant cytoplasm. And the second is monocyte. You can see the nucleus is horseshoe shape. It is horseshoe-shaped nucleus. Sometimes kidney-shaped nucleus is there, and this is monocyte. But you appreciate in the cytoplasm, there are no granules. These two are agranulocytes. Okay, we got it. So, total five types of WBCs are there. We got it. Granulocytes, these are of three types, and agranulocytes, these are of two types. So, it is Neutrophil, Eosinophil, Basophil, we see, and agranulocytes, we have lymphocytes and monocytes. So, total WBCs are there.

Now, the next question: where do they form? Where do they form? Tell me the organ. Of course, they all are formed in the bone marrow. Let me show you how they formed. So, you see this is the bone marrow. In the bone marrow, all the blood cells are formed. RBCs, WBCs, as well as platelets. All the blood cells are formed in the bone marrow. So, in the bone marrow, the first cell which gives rise to all the blood cells is known as hematopoietic stem cell. I call it the father, the ancestor of all cells. The hematopoietic stem cell is the father or the ancestor of all the blood cells. So, let me tell you, this is the hematopoietic stem cell present in the bone marrow.

Now, from this hematopoietic stem cell, you can see two arrows are coming. So, two cells are formed: one is myeloid stem cell or myeloid progenitor, or one is lymphoid stem cell or lymphoid progenitor. So, you can see myeloid progenitor and lymphoid progenitor. Progenitor is the stem cell. So, it gives rise to two stem cells, two lineages, two stem cells: one is myeloid stem cell, one is lymphoid. Myeloid progenitor, lymphoid progenitor.

Now, how many types of blood cells are there? Say, ma'am, there are three types of blood cells. We have RBCs, known as erythrocytes. We have platelets, okay, which are known as megakaryocytes. And we have WBCs, that is leukocytes. So, we have erythrocyte, megakaryocyte, and leukocyte. The three types of blood cells. And the WBCs are of five types, we have already seen. So, total five plus one plus one. So, total seven types of blood cells are present. We have to form all the seven, that is five WBCs, one RBC, one platelet, from these stem cells. So, how do they formed? How do they formed? Please understand first. If you have any query, please write down in the chat box. I'm having an eye on the chat box also. But if I'm in the middle of something, I'm explaining you, I will not interrupt that. Let me finish that portion, and I will come on your queries. So, don't worry if you have any query, just text it here, and as soon as I finish something I'm explaining you, after that I will come on your queries also. Okay. Okay, listen now.

So, as I told you, there are two types of progenitors: myeloid progenitor and lymphoid progenitor. So, myeloid progenitor gives rise to RBCs. All RBCs. It gives rise to all platelets also. All platelets. And there are five types of WBCs. Out of the five types of WBCs, you know, there is a cell which is formed here, is known as myeloblast. This myeloblast gives rise to four types of WBCs. Which four? Neutrophil, eosinophil, basophil, and monocyte, but not lymphocyte. So, all the RBCs are formed from myeloid. All the platelets are also formed from myeloid series. Out of the five WBCs, four of them are formed from the myeloid. Now, the one is spanning only one, that is lymphocyte, that will be formed from lymphoid, the lymphoid progenitor. So, same thing is written in front of you. Please understand. Please understand. If you don't understand things, you will not be able to understand the different types of leukemias. Please understand from the basic.

So, you can see it here. There is myeloid progenitor, which gives rise to all RBCs because it will give rise to erythroid precursor. It will give rise to RBCs. The platelets are also formed from the myeloid precursor only. Myeloid progenitor. And here is a cell formed which is known as myeloblast. What's the name of the cell? Myeloblast. Myeloblast gave rise to four WBCs. Out of the five WBCs, four are formed here: Neutrophil, eosinophil, basophil, and monocyte, but not the lymphocyte. So, only one cell. So, out of the seven cells, six are formed here only. The last one, the seventh one, it will be formed from the lymphoid progenitor, lymphoid stem cell. It gives rise to lymphoblast, and it gives rise to lymphocyte.

So, you can see the blood. You can see. So, all the RBCs, all the platelets, and maximum WBCs, I will use the word maximum, that is four out of five. So, four out of five, that is maximum WBCs, are from from the myeloid progenitor. So, can I call the myeloid progenitor as tri-lineage? Can I call? Say yes or say no? Yes, it is a tri-lineage. Tri-lineage means it is giving rise. It is giving rise to three types of cells. It is giving rise to RBCs also. It is giving rise to platelets also. And let's give it rise to maximum WBCs also. This one is not tri-lineage. And here, I guess you all can appreciate two types of blasts are formed. You have to understand the meaning of the blast. Myeloblast and lymphoblast. Myeloblast is from myeloid progenitor. Lymphoblast is from lymphoid progenitor. Myeloblast gives rise to these WBCs, and lymphoblast gives rise to lympho-lymphocyte only. Currently, I'm not interested in RBC. I'm not interested in platelets. To whom I'm interested? I'm teaching you leukemia. So, I'm interested in WBCs only. So, WBCs, all five WBCs are formed from blast. So, you can see this is the thing I taught you till now. You can see this is the hematopoietic stem cell. It gives rise to two stem cells: myeloid stem cell and lymphoid. The myeloid is giving rise to RBCs. It is giving rise to platelets, and it is giving rise to four WBCs out of five. And the lymphocytes are arising from the lymphoid stem cell. The same is shown to you in this figure also. Okay.

Now, the point is that they are not formed directly. Listen, listen, listen. I am interested in WBC, as I told you. So, I want to teach you how the lymphocytes are formed. It is not directly that lymphoblast gives rise to lympho-lymphocyte. There are certain precursors in between. You have to write down. You have to learn the intermediates. The same here also. I will, I will not teach you all four. I will take the prototype as neutrophil. So, I want to tell you how neutrophil is formed from the myeloblast. Tell me the intermediates here. So, in the same way, eosinophil, basophil, and monocytes are also formed, but we will not see all. So, I want to teach you two cells in detail: the neutrophil, how does they form from this myeloblast, and the lymphocytes, how do they form from the lymphoblast. You have to understand the intermediates in between, which are known as precursors. If you have understood this, believe me, leukemia will become a cakewalk for you. Believe me. Got my point?

So, you can see this is the precursors in between. It looks complicated. Don't worry, let me simplify it. Let me simplify it. So, I will simplify it. So, let's take neutrophil from here. I will tell you the precursors, and let's take the lymphocyte from here. I'm not teaching you the precursors of these three. They are likewise the same as that of neutrophil only. So, we will take a prototype from here, that is neutrophil. The point is that the neutrophil is formed from the myeloblast, and there are many intermediates in between, and the lymphocyte is formed from the lymphoblast, and there are certain intermediates in between. We have to see that intermediates, which are known as precursors. Got it?

Now, see, let's start from the beginning. So, again, you can see this is hematopoietic stem cell. So, two blasts are there: myeloblast, lymphoblast. Okay, let's take myeloblast first. Okay, I want to tell you from the myeloblast, how does neutrophils are formed? Tell me the intermediates. There are five intermediates in between. You have to learn the name of the connecting intermediates. From the myeloblast to neutrophil. Learn it. So, from the myeloblast, the first cell which is formed is promyelocyte. Then it is myelocyte. Then it is metamyelocyte. Then it is band form, and finally neutrophil. So, please learn the precursors. So, what are the precursors? First is myeloblast. Then promyelocyte, myelocyte, metamyelocyte. You can say it together: promyelocyte, myelocyte, metamyelocyte. Then band form, and finally neutrophil. In the same way, eosinophil, basophil, and monocytes are also formed. We will not see their precursors.

Coming on the other side, you can see we have a lymphoblast here. Lymphoblast gives rise to lymphocyte, but only one intermediate is there. There are not five intermediates, only one: prolymphocyte. So, this is the complete thing. So, the first cell is hematopoietic stem cell. It gives rise to two blasts. You have to understand blast. What is blast? We have two blasts: myeloblast, lymphoblast. Okay, myeloblast gives rise to neutrophil. Okay, I know it's also eosinophil, basophil, and monocyte, but I'm interested in neutrophil right now. And lymphoblast gives rise to lymphocyte. Tell me the intermediates. Who will tell me the intermediates? Myeloblast, promyelocyte, myelocyte, metamyelocyte, band form, and finally neutrophil. Okay, here lymphoblast, only one prolymphocyte, and finally lymphocyte. That's it. If you have understood this, if you have learned this, let's move ahead. Now you are ready to start with the leukemia. If you have understood the basics, the same thing is written in front of you. You can see, you can see myeloblast, it gives rise to promyelocyte. Myeloblast it gives rise to promyelocyte, then myelocyte, then metamyelocyte, then band form, then finally neutrophil. And you can see the lymphoblast, this one is lymphoblast, lymphoblast. This is prolymphocyte, and this is mature lymphocyte. The B lymphocyte and T lymphocyte, these are the two types. Everyone, give me a thumbs up in the chat box if you got the basics. If you got the basics, everyone, give me a thumbs up in the chat box, please. I request. So, if you got this, we will start leukemia right now. That was the overview. You now you can understand what is leukemia, what is blood cancer. How many of you got it? Give me a thumbs up. Come on. If you have any doubt, please you are open to ask. Don't hesitate. If you have any doubt till now, please ask it because if you don't understand this now, there is no use of the next ahead two hours sitting here and watching it or listening it because the complete leukemia is based on this only. Everyone got it? So, kindly give a gesture that you got it. Come on. Can we go ahead? Okay. So, let's start it.

So, I told you this is the precursors. Now, this is our master diagram. In this diagram only, I will teach you the four types of leukemias. Now, listen. I told you this is happening in the bone marrow. This is bone marrow, and this is blood. This is blood vessel. So, in my bone marrow, all these cells are present. These all are present. These all are present. In my bone marrow, hematopoietic stem cell is present, which is giving rise. So, all the precursors are present in my bone marrow. But in my blood, who is coming? Only the mature versions. The immature versions do not come in the blood, only the mature forms. So, from here, neutrophils are coming along with neutrophils. I know neutrophil, eosinophil, basophil, monocyte. I will consider all. They all are coming. Okay. But the mature forms. And from here, lymphocytes are coming. My point is that these are the mature cells. I mean to say, please understand, immature forms do not present in blood, but they are present in bone marrow. They are not present in blood, but they are present in. So, if you check my bone marrow or any healthy human bone marrow, you will find all these. But if you check my blood or any healthy human being's blood who don't have any blood disorders, any WBC disorders, you will find the mature WBCs in their blood, but not the immature ones. Okay.

So, this is the basic. Now, what is leukemia? This is leukemia. Leukemia is arrival of immature forms, especially the blasts, in the blood. So, once the blasts are coming in the blood. Oh my god. Blast. Which blast? Myeloblast and lymphoblast. If they are coming in the blood, it's leukemia. The immature blasts are coming in the blood. In acute leukemia, there are two types of leukemia: acute and chronic. In acute leukemia, the blast, the blast is the first cell. The first cell is the blast. Myeloblast and blast. They are coming in the blood. In acute leukemias. In chronic leukemias, the later, later precursors can also come in the blood. But it is the precursors which are coming in the blood. So, whatever is the leukemia, it is the precursors which are coming in the blood, except CLL. In CLL, blasts do not come. In CLL, mature lymphocytes are there which become abnormal because of the mutation. But in most of the leukemias, the blasts are coming in the blood. So, immature forms are coming in the blood.

Now, you may be thinking, ma'am, why, why they are coming in the blood? Usually, they don't come in the blood. Usually, the mature forms are coming in the blood. Now, you told us in a healthy human being, the mature forms are coming in the blood. Why these blasts are coming in the blood? We understood that once the blasts are coming in the leukemia, we understood that, but the question arises in your mind is why? You should ask this question, and why they are coming? So, the answer is mutation. So, in my myeloblast or in lymphoblast or in the other precursor cells, there are certain mutations which are taking place. Mutation. I will tell you the exact mutation also. Certain translocations, certain deletions, certain mutations in various leukemias. The mutations are different. Now, because of them, they become cancerous cells, and they start doing uncontrolled mitosis. You know, uncontrolled mitosis is the hallmark of cancer. Once the cell has the mutation, and because of that mutation, if the particular cell gets converted into a cancer cell, that cell will do uncontrolled mitosis and replace all other cells. Example, if this myeloblast, imagine this myeloblast, it is having certain mutation because of physical, chemical, or biological carcinogen. This myeloblast has certain mutation. Okay, not any other cell, only this myeloblast has certain mutation. So, this myeloblast will do uncontrolled mitosis, and it will replace all other cells, and it will be spilled over in the blood. I am using the word spilled over. It will be spilled over in the blood because it is too high. Normally, don't come in the blood, but sometimes if it is, it is too high, it is doing uncontrolled mitosis. It will be spilled. So, this cancer is known as AML. Sometimes lymphoblast does so. There is mutation in the lymphoblast. So, lymphoblast will do the uncontrolled mitosis, and it is spilled over in the blood. That is all. Sometimes all these cells will do uncontrolled mitosis. They all are spilled in the blood. Myeloid, myeloid precursor cells, it is known as CML. So, different cancers have different type of mutation. Ultimately, they convert into cancer cell, and because they convert into the cancer cell, they do uncontrolled mitosis, and because of the uncontrolled mitosis, they are spilled in the blood. And once they are spilled in the blood, it is known as leukemia, the blood cancer. The blood cancer, actually, the disorder is not in the blood. It's a misnomer. You can say the disorder is in the bone marrow. So, leukemias are the disorders of the bone marrow. There is a disorder in the bone marrow. In the bone marrow, certain mutations are taking place because of which the blasts or the precursors are spilled in the blood. How many of you got it? That is the basic. That is the basic.

Okay. Now, listen, one step further. What ahead? These blasts are coming in the blood. Sometimes they remain only in the blood. Okay. Like the chronic leukemias, they remain only in blood. Chronic myeloid leukemia as well as chronic lymphoid, CML as well as CLL, they remain in the blood. Okay. But sometimes in certain leukemias, after coming in the blood, they enter into the solid organ and form the discrete masses and many solid organs like liver, like spleen, like lymph nodes, producing producing various discrete masses. So, leukemias can give rise to lymphomas. Not always. Not always. Sometimes it is not necessary that all leukemia convert into lymphoma. Not no. Sometimes they do so. And not all leukemia. It happens in AML. It happens in ALL, like more frequently, but not in others. CML may not happen. How many of you got it? How many of you got it? So, sometimes leukemias can give rise to lymphomas, not always. Mind my words. So, this is the basics. If you got. So, this is known as organ infiltration. Organ infiltration. So, normally, the summary is that the normally the blasts are present in the bone marrow. I'm, I'm a healthy human being. I don't have any WBC disorder. So, in my bone marrow, the blasts are there. Myeloblast is also there. Lymphoblast is also there, but they are present in my marrow, they are not present in my blood, they are not present in my organs. If the blast, if the myeloblast or lymphoblast, they because of the mutation, they become cancer cell, and they do uncontrolled mitosis. Because of the uncontrolled mitosis, they become too high in number. They replace all other cells, and they are spilled in the blood. Once the blast come in the blood, it is known as leukemia. In the acute leukemia, sometimes in chronic leukemia, along with the blast, the the immature versions also come. Okay, the later precursors also come. This is the early precursor in the series. The earliest precursor in the series is blast. Got my point? And after coming in the blood, but not always. Sometimes they infiltrate in various organs, and leukemia can convert into lymphoma, sometime, not always. Mind my words. I hope you all got it. I hope you all got it. Say yes if you got it.

So, let's classify leukemia. Let's classify leukemia. It's very easy. Listen. Listen. Now, the complete thing is depending which blast is coming. Which blast is coming? This is a simplified version of leukemia. I'm telling you the classification. Which blast is coming? Is it lymphoblast or is it myeloblast? Which blast is coming? If lymphoblast is coming in the blood, it's known as lymphoid leukemia. The leukemia is lymphoid. If myeloblast is coming, it's myeloid. It's myeloid leukemia. Okay. One of the blast is coming in the blood. Lymphoid, lymphoid blast is coming, lymphoid leukemia. Myeloid blast is coming, leukemia. Each of them can be acute, can be chronic, can be acute, can be chronic. So, basically, we have four types, four types of leukemia. What are the four types of leukemia? Can you see? Can you see the names? Say acute lymphoblastic leukemia, ALL. Chronic lymphocytic leukemia, CLL. Okay. Acute myeloid leukemia and chronic myeloid leukemia. So, you can see ALL, CLL, AML, and CML. How many of you got it? These two are myeloid in origin, and these two are lymphoid in origin. So, total four leukemias are there in our syllabus. We will compare them one by one. No, it is not always. I'm saying that Bisma is saying that lymphoma is always after leukemia. No, it's not necessary. Sometimes the blast originate in the solid organ. So, lymphoma is the first thing happening, and it will spill over in the blood, leading to the leukemia. It is not necessary that leukemia gives rise to lymphoma. Sometimes lymphoma can also give rise to leukemia, and sometimes they are de novo only. Leukemia is there, or only lymphoma is there. It is not necessary that they are occurring together. My point is that in leukemia, it's a blood cancer. You will not find any discrete mass in any organ. But in lymphoma, you will find the discrete masses in various solid organs. So, lymphoma is a tumor of solid organ, but leukemia is a cancer of the blood. How many of you got it? You got it, Bisma? You got it? Okay. There can be other reasons also for the lymphoma. So, I will take one session on the complete lymphomas. So, I will schedule all lymphomas in one shot because many students after this session have demanded that ma'am, after leukemias, we want one session on lymphomas also. Hodgkin's lymphoma as well as non-Hodgkin's lymphoma, all lymphomas in one shot. I'm going to schedule it. Do you want it? If you want it, we will schedule it soon. Okay, very soon we will schedule it. So, let's continue with the leukemias right now. Okay.

So, this is the classification of the leukemias. You can see leukemia is of two types: lymphoid and myeloid. Here, lymphoblast is coming, and here, myeloblast is coming in the blood. Each of them can be of two, two types: acute, chronic, acute, chronic. So, finally, we are having four types: ALL, CLL, AML, and CML. These two are myeloid. You can see myeloid, and these two are lymphoid. So, these are the four types.

What are acute and chronic? In acute, in acute leukemia, whether it is myeloid or whether it is lymphoid, the blasts are coming. Either myeloblast is coming or lymphoblast is coming. How much blast is coming? So, I told you now, this is the myeloblast. Normally, in the bone marrow, in the bone marrow, this is the myeloblast. This is the lymphoblast. The blasts are less than 5%. Normally, in a healthy adult human being, the blasts are less than 5%. Now, due to mutation, either myeloblast is doing uncontrolled mitosis, or due to mutation, lymphoblast is doing uncontrolled mitosis. So, if their percentage becomes more than 20% of all the cells, more than 20%. If each of them can be more than 20%, it is known as acute leukemia. So, the definition, the WHO criteria for leukemia is blast more than 20%. You may be asking, ma'am, which blast? It can be myeloblast, it can be lymphoblast, any of them. So, if myeloblast is more than 20%, I will call it AML, Acute Myeloid Leukemia. If lymphoblast is more than 20%, I will call it. So, this is the definition of the acute leukemias. Please learn it by heart. How many of you got it? So, this is the WHO criteria. WHO criteria is more than 20%, and FAB criteria, you know, there are two different organizations, WHO and French American British. So, both of them now, some people follow this classification, some follow. So, WHO has given a cutoff of 20%. If the blast in the marrow is more than 20%, it is known as acute leukemia. If the blast is more than 30%, it is known as acute leukemia. This is according to FAB. So, according to WHO, the cutoff is 20%, and according to FAB, French, American, British, it is 30%. So, anyone can be asked in your exam. So, two different bodies have given two different cutoffs. Okay. So, usually, we consider the WHO. So, please, according to WHO, the criteria for the acute leukemia is 20% blast minimum, 20%, more than 20%. Okay. Normally, it is less than 5%. How many of you got it? Got it. So, this is the definition of acute leukemia. I taught you two definitions: Acute Myeloid Leukemia, that is myeloblasts are more than 20%. And Acute Lymphoid Leukemia, that is lymphoblasts are more than 20%. Got it? So, that is the thing. Chronic leukemia, in chronic leukemia, blast may come, but basically, the later precursors come in the blood. So, there is no cutoff in the chronic leukemias, and each of them can be myeloid, lymphoid, myeloid, lymphoid. So, AML is Acute Myeloid Leukemia. ALL is Acute Lymphoid Leukemia. CML is Chronic Myeloid Leukemia, and CLL is Chronic Lymphocytic Leukemia. So, that is the thing we got it. So, ultimately, the thing is which blast is coming in the blood. So, you should be able to differentiate what is coming in the blood. Is it myeloblast or lymphoblast? Both of them look differently. So, you should be aware of the morphology. How does myeloblast look, and how does lymphoblast look? You must be aware of that. How does myeloblast look, and how does lymphoblast look? You should be aware of that. Got it? So, you should be aware of the morphology of both of them. Got it? Myeloblast is a little bit larger, and lymphoblast is a little bit smaller. You can see in the diagram itself. Don't learn. See in the diagram here, the cytoplasm is moderate. You can see moderate amount of cytoplasm. You can appreciate, but hardly any cytoplasm. You can see a peripheral rim, small rim of cytoplasm. It's smaller with no cytoplasm or scanty cytoplasm. The most important difference here is the Auer rod. Here, Auer rods are maybe present. Not always, but you can find the Auer rods here. Auer rods are always absent. Auer rod is a red color rod-like thing which is a concentrate of the granules. The granules are aggregating and forming a rod-like material which is known as Auer rod. So, Auer rod is present in myeloblast. They are not present in lymphoblast. Please learn. Auer rod is the biggest difference you can see. Okay. Got my point? Got my point. So, that is the thing you can see here. So, that is the classification.

Now, we have four types of leukemia to be covered now. So, I request all my dear students to take out your notebooks, to take out your pen, and make this comparative table with me. I will teach you four leukemias one by one in a fixed set of headings. I will start with CML. Okay. Then I will teach you AML. So, myeloid will be done. First, we will deal with the myeloid. These two are myeloid leukemias. Then we will come on the lymphoid ones. In the lymphoid one, first I will teach you acute, and then chronic. So, sequence is this because I want to compare these two, the acute versions of the two together. That's why first I'm telling you the myeloid one, first chronic, then acute, and then the lymphoid one, first acute, then chronic. So, this will be my sequence because I want to compare these two back to back. That's why I'm telling you this sequence. Now, in each of them, first I will let you know the definition of each of them. You should understand. Age group is very different. So, you know, you get MCQs, and you will get an age. So, reading the age only in your question will give you, you know, a differential diagnosis. They are talking about which type of leukemia. So, you have to concentrate on the age. Age is always important. The most important is the mutation. Which exact mutation is there? In each of them, you have to learn the mutations. Then classification, if applicable. So, I will tell you the FAB classification here and here, AML and ALL. The FAB classification, you have to learn. French, American, British classification. Clinical features, you have to understand. Lab diagnosis, you get many questions on that. Treatment part, I will deal here only. The medicine part also, and the prognostic factors, you get many MCQs on prognosis. Believe me. And not only this, in the end, we are going to compare all. Okay, got my point? We are going to compare all four together at one place, in one shot. So, that the thing will be oversimplified. So, if you make this table with me, it will be useful for you that after the session, you can revise all the leukemias in just five minutes by looking at this table. I can guarantee you, all your MCQs can be cracked from this table. Take my challenge. Okay. So, let me summarize it, and it will be given in the notes also. After the session, I'm going to provide you the PDF. If you don't want to make this table, it's okay. It will be provided in the PDF. So, it's your choice. So, can we go ahead? Can we start? So, let's start with the first one. Let's start with the first one. CML. Let's start with CML. Can I start? So, let's start with CML. The first one. So, what is the definition of CML? Let's start with the introduction. The definition of the CML. What is CML? There are four criteria. If any human being, any adult person, aa, what is the normal WBC count in our blood? We have RBC, we have platelet, and we have WBC. This is the normal three cells present in the blood. Tell me the normal count of all three. Normal adult human being, normal. So, RBCs are 4.5 to 5.5 million per microliter or per deciliter. Okay. Platelet is four to five, four to five lakh, not million, lakh per deciliter. WBCs are 4,000 to 11,000 per deciliter. Now, see, see the normal range. The WBCs are in thousands. 4 to 11. The platelets are in lakhs. Okay. 4 to 5 lakh. And I'm sorry, not 4 to 5, you can say 1.5 to 4 lakh. 1.5 to 4 lakh. I'm sorry. And here, the RBCs are 4.5 to 5.5 million per deciliter. So, that is per deciliter. You can see now. I'm concerned with WBC right now. Okay. In all the leukemias, and most of the leukemias, the WBC count will be high. That is known as leukocytosis. So, imagine an adult human being in which the WBCs are, the WBC count is high. The WBC count is high. It is usually normally it is 4,000 to 11,000, as I told you, 4,000 to 11,000. Here it will be nearly 2 lakh. WBCs are 2 lakh. Imagine 11,000 is the highest limit. Here it is in lakhs, one lakh, two lakh, three lakh, like that. So, it is high. It is high. But these are not mature. These are the immature ones, not the mature mature neutrophil, eosinophil, basophil, monocyte. They are very less in number, very less. But their precursors are more. Okay. So, that is the first criteria. That is the first criteria. So, in total count, total leukocyte count, TLC, the count is high. And in DLC, you will find these are immaturities. These are not the mature ones. The first criteria: basophils are too high. The splenomegaly is there. The patient's spleen is enlarged, and Philadelphia chromosome is positive in 95% of the patients. Philadelphia positive. What is Philadelphia? I will tell you. So, learn the four criteria of CML. So, introduction may, I'm sorry, introduction may write down the four criteria. The four criteria of CML. You should know the four criteria. You get a question on the criteria also. So, there are four criteria. What are the four criteria? Number one, WBC count is high, leukocytosis with immaturities. With immaturity is the first foremost, most important criteria, out of which basophils are there. Basophils are really high. Number three, spleen is enlarged. Splenomegaly is there. Number three. And number four, Philadelphia chromosome is positive. I will tell you what it is. Wait a while. Okay. That is the four criteria. What about the age? It occurs in middle age or old age, after 50 years, usually after 50 years, usually. So, you will get a question. There is a 50-year, 55-year, 60-year male, female, whatever like that. So, middle to old age. So, it is after 50 years.

Now, coming on the pathogenesis. Look at here, everyone here on the screen. I am teaching you CML. I'm teaching you the pathogenesis of CML. So, it is a leukemia arising from the myeloid origin. So, here the problem, here in these precursors will be there. The problem is not there in the lymphoid precursors. The problem will be in the myeloid precursor. That we got it. Okay. We got that. Now, what are the myeloid precursors? We have five precursors. We have myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form. And neutrophil. These are the cells. You can see these are the cells. These all cells have the nucleus, and inside the nucleus, they have the DNA. Now, because of physical, chemical, or biological agents, they got mutated. They all got mutated. They all got mutated. Now, tell me, this is the human cell. Any human cell. This is the nucleus of the human cell. How many chromosomes we have? We all know that we all have diploid cells, that is 46 chromosomes. Say yes or no. Instead of saying 46 chromosomes, why don't you say 23 pairs? 23 pairs is a better thing to say. So, this is pair number one, pair number two, pair number three, pair number four, five. Likewise, 23 pairs are there. I'm not interested in all pairs. I'm interested in two pairs. Pair number 9 and 22. So, on the next page, I'm drawing two pairs. Okay. So, let's draw a cell. Okay. Let's draw the nucleus of the cell. Inside the nucleus, I'm drawing only two pairs. This is pair number nine, and this is pair number 22. I'm interested in two. Which two? This is nine. This is 22. Okay. You will see, ma'am, which cell is it? Which cell? It can be one of the five cells. I don't know. It can be myeloblast. It can be promyelocyte. It can be myelocyte. It can be metamyelocyte. It can be band form. The mutation is occurring in all five. In all five, the five precursors of the myeloid series. Okay. So, listen what is happening. Normally, in me, in you, in all the adults, human beings, healthy human beings, on chromosome number nine, there is a gene. The name of that gene is ABL. That is a gene that is normal. It is present in me, you, everyone. The name of that gene is ABL gene. We all have that. It's normal. So, it is doing its normal function. The normal function is mitosis, but under control. So, whenever the growth factor is coming, then only the cell is dividing, otherwise, cell is not dividing because of ABL. On 22, we have another gene. The name of that gene is BCR. We also have it. Have it. I have, you have, we all have it. It is also normal gene. So, again, here it also helps in mitosis. This also helps in mitosis. This also helps in mitosis, but mitosis under control. So, whenever the growth pattern will come, then only they will do the mitosis, otherwise, they will not do the mitosis.

Now, due to physical, chemical, or biological agents, there is translocation. What is translocation? A portion of the two chromosomes, they will exchange with each other. So, here nine will give this portion to 22, which contain the ABL. So, ABL, which is normally present in nine, it is going to 22. It is going to 22. So, ABL will reach here. ABL will reach here, and it will fuse with BCR. BCR is already present on 22. So, ABL will fuse with BCR. Say yes. ABL will be fusing with BCR. So, a new gene is formed. The fusion gene. It is known as fusion gene, ABLBCR fusion gene, or ABLBCR hybrid gene. Fusion or hybrid gene that will lead to uncontrolled mitosis. Not the cell is cancer cell because of this deadly gene. This deadly gene, the fusion gene or hybrid gene, it will form an abnormal enzyme. The name of that enzyme is tyrosine kinase. Tyrosine kinase, abnormal tyrosine kinase, that will do the uncontrolled mitosis. This cell goes on dividing, goes on dividing, from 1 to 2, 2 to 4, 4 to 8, 8 to 16, 16 to 32, 32 to 64, so on, and they will be spilled in the blood. So, all these cells will be spilled in the blood. Got my point? Normally, they are not present in blood. They are present in marrow. But they will replicate, replicate. They will do the mitosis. They will pull the marrow. They will replace all other cells in the marrow. And after filling the marrow completely, they will be spilled in the blood. Got my point? This is CML.

You will, you should be thinking, ma'am, that you said that it's translocation. Translocation is balanced here. So, here nine is giving ABL to 22. What 22 is giving to nine? 22 is giving to nine a portion of chromosome which don't contain any important gene. Which don't contain any important gene. So, that portion is given to nine. So, basically, the fusion is formed on 22. The fusion gene. That's why chromosome number 22 is known as Philadelphia chromosome. Philadelphia chromosome. This chromosome is known as Philadelphia chromosome because the fusion gene is formed here. Got my point? How many of you got it? So, this is the fusion gene which is formed on 22. So, on chromosome number 22, in a patient with CML, we get a gene that is a hybrid gene or fusion gene where the two genes are fusing with each other: ABL and BCR. Normal adults don't have this fusion gene. I'm having ABL, but my ABL is on nine. I'm having 20 um BCR, but it's on my 22. I don't have ABL-BCR fusion. The patients with CML have it. How many of you got it? That will lead to abnormal tyrosine kinase, and that will lead to uncontrolled mitosis.

Now, what if I want to treat this patient? Let me tell you the treatment here only. I want to treat this patient. So, basically, I will give targeted therapy. The name of that targeted therapy is imatinib. Have you heard the name? Imatinib has a special role because it is the first targeted therapy discovered in the world. There are many targeted therapies now available for the cancers, but it is one of the first, you know, it is the first targeted therapy which was discovered. Okay. So, imatinib is the name of the drug. The most important thing, it's an oral tablet. It is available in oral form. So, patient has to take one tablet daily. Patient don't have to hospitalize, go to the hospital and take long chemotherapy. No, no. It's the chemotherapy only, but the patient will take in the form of the tablet. Easy to take. The route of administration is easy. So, patient has to take one tablet daily. Okay. And what does this imatinib will do? Imatinib will do the apoptosis of all those cells in the bone marrow which is having this fusion gene. All those cells will undergo apoptosis. Apoptosis. And imatinib will inhibit the abnormal tyrosine kinase. So, imatinib will control CML. After the discovery of imatinib, the prognosis of CML is very good, very good. Hardly any patient have any adverse effect or any poor prognosis. Okay. Because of the discovery of imatinib, before that, we used to do bone marrow transplant and other chemotherapy drugs that were not very successful, but imatinib is a real game-changer in case of CML. Are you getting it? Are you getting it? Say yes or say no. Say something. But respond, people, respond. It's a live session. Keep interacting. Got it. Got it. Can we go ahead? So, this is the complete story for CML. So, tell me, what is happening? Say, ma'am, we understood this master diagram. Now, in this diagram only, I will teach you whole leukemia. Please understand. I taught you the first one. The pathogenesis of the first one. You tell me, what is happening in the first one? Say, ma'am, in these five cells, can you enumerate the five cells? Say, ma'am, myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form. In these five cells, 9-22 translocation is taking place. 9-22. We write it like this: 9 semicolon 22, and we make a small bracket, and we write down a small T. It's a convention. We write like this only. It means that there is the exchange between 9 and 22. So, that is the translocation, balanced translocation. Or instead of that, you can write down the name of the gene itself. On 9 is the number of the chromosome, 22 is the number of the chromosome. On them, name the gene. So, you can say ABL-BCR translocation. It is also good to say ABL-BCR 1 and the same thing. Whether you say 9-22 or whether you say ABL-BCR, the meaning is the same. Got it? So, basically, in these five cells, this is happening: 9-22 translocation or ABL-BCR translocation. Because of that, they all five are doing uncontrolled mitosis because abnormal tyrosine kinase is formed in all five. So, these five are doing uncontrolled mitosis. Because of the uncontrolled mitosis, these five are spilled in the blood. So, these five are coming in the blood. So, myeloblast in the blood. What, what is coming? Myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form, along with a little bit mature form: neutrophil, eosinophil, basophil, and monocyte. But they are very less. Maximum of them are immature forms. So, if you take the blood sample of this patient in a test tube, what do you find? What do you find? You will find maximum are WBCs. WBCs are nearly two lakh or three lakh. But you see, they are not the mature ones. Maximum of them are immature. Maximum of them are immature ones. How many of you got it?

So, what is the um, what is the function of WBC? Why God has provided us with WBC? So, WBCs do the defense. They are like army. The God has provided us the army. So, you may be thinking, normally how much army I'm having? I'm having 4,000 to 11,000 soldiers in my army. How many soldiers I'm having? Adult human being, healthy human being have 4,000 to 11,000 soldiers in the army. Here, the person is having two lakh soldiers in the army. You see, the person will be super immune. No, no, no, no. These are these are immature ones. These are not mature soldiers. These are not mature forms. These are immature ones. So, person is prone to infection. You will see, ma'am, the two things are contradictory. Yes, it is a paradox. Although the person is having high WBC count, still the person is having high susceptibility of infection. You will see, ma'am, how the two things together? You are saying higher WBC count, still person is high susceptibility of infection. Yes, the answer is immaturity. They are high, but they are immature. They don't do their function properly. So, that's why the person is having high susceptibility of infection. All leukemia patients have high susceptibility of infections. Got it. Soon I will cover MPN and MDS also. A gap. I will cover one by one. We will cover. Okay. Can we go ahead? How many of you got it? Okay. So, the same thing is shown to you. Normally.

ABL is present on 9, and the BCR gene is present on 22. Okay, now let me show you this side. Concentrate on this side. This is normal. Don't see the translocation right now. See the uh, left-hand side first. See, this is a pair of 9. You can see the two chromosomes. And this is a pair of 22. See the two chromosomes. I want to highlight the one gene on each of them. I want to highlight 9 has ABL, concentrate, and 22 has BCR. So, it's normal. They are doing their responsibility normally. They are doing their function normally. ABL on 9, BCR on 22. Everything was good to go. Everything was good to go.

But now, because of translocation, you can see what is happening. See, 9 ABL is going on 22, on which BCR is already there. Now you can see on the 22 what is happening. On the 22, there is a fusion gene that is formed. Can you appreciate the fusion gene or hybrid gene? Because BCR was already there, and ABL is also coming, and this is deadly. That will lead to uncontrolled mitosis. In exchange for that, the 22 is giving a portion to 9 that doesn't contain any important gene. So, this is translocation. How many of you got it? How many of you got it?

So, what is happening in translocation? So, if you're going to write in your exam now, like if you have a theory exam, write down in the form of a project, and if you have to solve MCQs, it will be easy to solve. Now, ABL is present on 9. Normally, it got translocated to 22. On 22, we already have BCR. So, ABL-BCR hybrid gene is formed that is known as Philadelphia chromosome. So, 22 is Philadelphia, not 9. It's a very important MCQ. It's a very important MCQ, and that will lead to abnormal tyrosine kinase, that will lead to uncontrolled mitosis, and that will lead to CML. So, this is the complete story of CML.

Okay. So, in CML, all these cells are doing uncontrolled mitosis, and because they are doing uncontrolled, the five cells: myeloblast, promyelocyte, myelocyte, metamyelocyte, and band, they are doing uncontrolled mitosis. So, they are replacing everything else in the marrow. Everything else in the marrow, they are replacing. Once the marrow is full, full, they are spilled in the blood. They are spilled. I'm using the word spillage. They are spillage. They are spilled in the blood. So, in the blood also, you get all five. You will get myeloblast, promyelocyte, myelocyte, metamyelocyte, band form, and along with a few mature versions: neutrophil, eosinophil, basophil, and monocyte. You will get all this in the blood. All this in the blood. So, if you make a slide, if you take a slide and make a smear, if you make a smear of the blood sample here, if you make a peripheral smear, you will get all these cells. You will get all these results. It is typically known as garden party. Garden party. Have you ever visited a garden party? Garden party, everyone is in a different dress. It's not school uniform. In school uniform, everyone is in the same uniform, the same dress, the same dress code. In a garden party, everyone is in different beautiful dresses. So, you are getting different types of cells. So, this typical appearance of CML is known as garden party appearance. It's a way to remember. It's a way to learn.

Okay. Uh, Sachi, I'm coming on this 210 kilodaltons intentionally. I have skipped it. Let me tell you, when I will teach you the AML, I will teach you this, because in AML also there will be 9-22 translocation, but the size of that fusion gene will be different. There it will be 180; here it is 210. I will help you learning there, okay? Got it? Can we go ahead? If you got it, okay.

So, as I told you, all these cells are coming in blood, but the most important is blast. Which blast? Myeloblast. Based on the blast, there are three phases in CML. There can be chronic phase, accelerated phase, or blast phase. You can learn the mnemonic CAB: Chronic, Accelerated, Blast. Cab. There is chronic phase, there is accelerated phase, and there is blast phase. So, how much myeloblast? If myeloblast is 10%, less than 10%, it's chronic. 10 to 20%, it's accelerated. And more than 20%, it's blast phase. So, in blast phase, the patient is highly symptomatic. How many of you got it? So, based on that, we give the uh, based on the blast percentage, we give the phase in which phase of uh, CML, the patient is. It is a triphasic leukemia. We can see it's the, it's the leukemia which is triphasic. So, that is the pathogenesis. How many of you got it? Give me a thumbs up if you got the pathogenesis. What is happening? Everyone got it? What is exactly happening in the CML? CML is a leukemia. So, CML is a blood cancer. The people, the students, the audience who can understand this master diagram can understand everything. So, let's start from the basic. If you missed the initial part of this lecture, now, please go and first watch the initial lecture. First understand how the RBCs are formed. Got it? Then only you can understand this. So, basically, in CML, the precursors of the myeloid series, that is these five precursors, they have mutation in them. So, name the mutation: 9-22 translocation or ABL-BCR translocation. Because of this translocation, they become cancerous cells, and they are doing uncontrolled mitosis, and they are all spilled in the blood. So, in the blood, all five are present, and that is the, um, we got the pathogenesis.

With this pathogenesis, coming on the clinical features. Now, clinical features are due to bone marrow failure. I'm saying, now you understand this diagram also. I have explained you at the beginning of the lecture. In the bone marrow, RBCs are also formed, platelets are also formed, and you know, myeloblast is also formed from the common myeloid progenitor. Common myeloid progenitor. RBCs, WBCs, platelets, they all are forming. Now, I'm saying there is mutation in the myeloblast. So, myeloblast and their precursors are doing uncontrolled mitosis. So, they replace everything else. They replace everything else. They replace the RBC also, RBC and their precursors also, erythroid precursors. And they replace the platelet or megakaryocyte precursors also. So, patient has anemia because RBCs are not formed. Patient has thrombocytopenia because platelets are not formed because it is replaced by the myeloblast. Myeloblast and their precursors, the five cells. Which five cells? Myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form. They are doing uncontrolled mitosis. So, the complete marrow is filled with these five cells, and all other cells are replaced. So, no RBCs are formed or very few RBCs are formed. No platelets are formed or very few platelets. So, patient has anemia. So, patient will come to your doctor, "I'm having lethargy, pallor, fatigue, you know, lack of energy." Due to the anemia. Patient has multiple bleeding disorders like patients have bruises, epistaxis, bleeding from the gums, bleeding from the nose, it's epistaxis, bleeding from the ears, or internal bleedings. So, because of thrombocytopenia. Okay. And you will see WBCs are too high. But still, patient is highly prone to infection. Because I agree, WBCs are too high. Instead of 11,000, they are two, three lakh. I agree. I totally agree. But they are immature. So, they will not do their function. So, person is having anemia, bleeding disorder, and infection. So, technically, the person is presenting like pancytopenia. Although RBCs are less, okay. Platelets are also less. Okay. But WBCs are not less. In pancytopenia, WBCs are too high here. So, because RBCs are less, patient has anemia. Because platelets are less, patient has thrombocytopenia or bleeding disorders. But WBCs are high. Still, patients have high propensity or susceptibility for infection because of the immature forms. Okay. Apart from that, there is hypermetabolism. The cells are formed more. They are, they are like, you know, they will be dead more. So, there is weight loss, night sweats, anorexia, splenomegaly is massive. All these cells will go. The immature cells which are there in the marrow, uh, they are spilled in the blood. They will go in the spleen, and they are trapped in the spleen. So, patient presents with a massive splenomegaly. You got my point? So, this is the blood vessel. Okay. This is a blood vessel. In the blood vessel, normally 4,000 to 11,000 WBCs are present. But now there are two lakh WBCs are present. So, via blood, they all will be moving to the spleen, and they are trapped in the spleen, and that's why the spleen will be enlarged, and that is splenomegaly. This is the reason for hypersplenomegaly. So, please understand everything. Don't mug up. Please understand everything.

Now, coming on the lab diagnosis of CML. In the lab diagnosis, not only of CML, of all leukemias, there is a fixed format. So, I will tell you the lab diagnosis in these headings only. First, tell me what will be the change. Take the blood sample of the patient. Aspirate the marrow. Take the bone marrow biopsy as well as bone marrow aspirate. Do the cytogenetics by doing karyotyping. Okay. Do the cytochemistry. That is the special stain. Cytochemistry means special stain. Cytogenetics means karyotyping. You are doing the karyotyping. The genetics, the molecular studies, and others are not important. So, blood study, bone marrow study, genetic study, and special study. By these four things, we will do the diagnosis of all leukemias. How many of you got it? How many of you got it? Okay.

So, in the blood, we will see three things. What happened to hemoglobin? Obviously, hemoglobin will be less because RBCs are less because the RBCs and platelets are replaced by the immature WBCs. So, that's why less hemoglobin, less platelets, but WBCs will be too high. I know. So, patient has anemia. RBCs are less, hemoglobin is less. Patient has thrombocytopenia. The platelets are less. Patient has bleeding. And WBCs are nearly two lakh instead of 11,000, it's two lakh. But, but, but add a but here. They all are immature forms. You can see the diagram. See the diagram. How many types of cells you can see in this diagram? I can appreciate this is an eosinophil because it is having red granules. This is a basophil because it is having the bluish granules. And this is a neutrophil, the adult, the mature neutrophil. I can see the multilobated nucleus with the pink, pink granules. This is a band form. This is a promyelocyte. This is a metamyelocyte. Likewise. So, I'm getting an abundance of cells. I know. So, I'm getting all these five cells in the blood along with the neutrophil, eosinophil, basophil. So, this is the diagram. You can see this one. You can see this one. So, appreciate you are getting basophil, you are getting eosinophil, you are getting neutrophil, you are getting all other cells also. The band forms are usually, you can identify. They are C-shaped. The nucleus is C-shaped. The C-shaped at the band forms. You can see these all. So, you can, how many cells you can see? Say, "Ma'am, I can see promyelocyte, myelocyte, metamyelocyte, band form, basophil, neutrophil, eosinophil, and the myeloblast." You get the myeloblast. This is known as garden party appearance. What is it known as, people? It is known as garden party. What do you mean by garden party? In garden party, everyone is in a different dress. So, garden party appearance. Typical appearance of CML. Never forget. So, out of the four leukemias, I have finished one. I have completed one. Three more to go. In the end, you can understand the peripheral smear of all four. But currently, let's have a look of CML. In the CML, appreciate the word, "Ma'am, there are four types, five types of cells: myeloblast, promyelocyte, metamyelocyte, band form, along with neutrophil, eosinophil, and basophil, and monocyte." So, this is garden party. And you can appreciate it in the diagram. Now, you will appreciate once I will cover all four, and you can make out the differences. Okay. Currently, CML is. So, blood picture, I told you. The WBC peripheral smear also we have seen.

Now, coming on the bone marrow. In the bone marrow, tell me the cellularity. The cellularity. I told you what is happening in the bone marrow. In the bone marrow, the myeloblast is doing uncontrolled mitosis. So, obviously, cellularity is more as compared to a healthy individual. The myeloid cells will be more. The other cells are not more. So, erythroid cells are less, megakaryocytes are less, and overall myeloid cells are more. Out of the three, myeloid are abundant. Erythroid and megakaryocyte are less. So, that is the bone marrow. Obviously, you can understand it. So, we have seen the blood picture. We have seen the bone marrow picture.

Now, see the genetics. If you see the genetics, you will typically get 9-22 translocation. You will get it. And this is a confirmatory diagnosis, but it's very expensive. But if it is done, it is confirmatory diagnosis. So, we can confirm it via cytogenetic stereotyping, 9-22 translocation. Cytochemistry is a special stain. It's a type of stain. It's a special thing. It's a special stain. Okay. What is the special stain? Here, we use the name of the stain is Neutrophil Alkaline Phosphatase. NAP or also known as Neutrophil is a type of leukocyte. No, leukocyte is WBC. It is known as Leukocyte Alkaline Phosphatase, LAP. So, whether you say NAP or whether you say LAP, the meaning is the same. What do you mean by NAP or LAP? Neutrophil Alkaline Phosphatase or Neutrophil is a type of leukocyte only. Leukocyte is WBC. There are five types of WBC. So, Leukocyte Alkaline Phosphatase. You say, "Ma'am, what does it mean? What does it mean?" It, it is a stain that will highlight the granules. The granules. You tell me. You tell me. This is the complete series. Okay. These are, this is neutrophil. You know, neutrophils have granules in the cytoplasm. Yes or no? So, but, but its precursors don't have granules. Granule formation starts from promyelocyte and myelocyte, and they have less granules, gradually increase, and maximum granules are present in neutrophil. Maximum granules are present in neutrophil. The precursors have less granules. So, I'm saying that in CML, the precursors are coming more in the blood. I know the precursors are more. The myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form are coming more in the blood as compared to adult neutrophil. Adult neutrophil is there, but it's less. So, you tell me, what happens to the NAP score? NAP score in CML. The NAP score will be more as compared to normal or less as compared to normal? Normally, the NAP score is due to adult neutrophil. Here, adult neutrophils are less. So, NAP score will be less because the granules are less. The precursors don't have granules. So, NAP score will be less. So, in CML, the NAP score is less, not more. So, please learn the NAP score here. What is NAP score? The NAP score in CML, the NAP score is reduced. How many of you got it? How many of you got it? Okay, say yes if you got it. So, this is the reason why the NAP or the LAP score students learn it, but they don't understand why the NAP or LAP score is reduced in CML. It is not increased. Highlight it. It is reduced in CML.

Now, the most important differential diagnosis of CML. We are done with the diagnosis. Okay. We have seen the blood picture, bone marrow picture, cytogenetics, and cytochemistry. Here, the NAP score is reduced. We have seen that others, uric acid will be high because there are more and more cells, they are forming, and more and more cells are dying also. Whenever cells burst, they are dying, the uric acid will be more. So, patient presents with gout or hyperuricemia. We got it. So, this is the complete diagnosis.

Now, coming on the differential diagnosis of CML. In CML, the most important differential diagnosis is leukemoid reaction. What do you mean by leukemoid reaction? Leukemoid reaction is a condition in which if you check the WBC count in the blood, it is nearly 50,000 to one lakh. It is not more than one lakh. Never. It is 50,000 to one lakh. Okay. Normally, it is up to 11,000, but it's not cancer. It's not leukemia. So, sometimes you can get confused. Is it CML or is it simple leukemoid reaction? Leukemoid reaction is not cancer, you know. So, whenever, you know, there is a human being, this is the blood vessel of the human being. In the blood vessel, WBCs are there. These are the WBCs. Normal count, I told you, it's 4,000 to 11,000. Okay. Now, whenever any infectious organism, like bacteria, virus, fungus, parasite, or any malignant cells, or anything, any foreign particle, okay, it is entering in the blood, what happens? This, the army, now they will increase. They will increase. So, instead of 4,000 to 11,000, they will increase, increase, increase, and they will become nearly 50,000. So, it's reactive. It is reacting in response to exogenous agents. Okay. It's not cancer. Here, mutation doesn't happen. It is leukemoid reaction. Leukemoid reaction happens in response to infection. In response to infection, sometimes the WBC count is too high, but it's never more than one lakh. It will be nearly 50,000, maximum up to one lakh. But never more than one lakh. It will never cross one lakh. In CML, it is two lakh, three lakh, like that. How many of you got it? This one is reactive. That is leukemoid reaction. It is excessive leukocytosis. I mean, increase WBC count in the peripheral blood that resembles CML, but the patient doesn't have CML. So, don't start emitting here. Being a doctor, don't get confused that you are doing the CBC. In the CBC, you got a WBC count as too high. It is nearly 50,000, 60,000, or one lakh, and you cannot make the diagnosis. "Oh my God, it's CML. Start." No, no, no. First, do the cytogenetics. Confirm. Is it 9-22 translocation? Yes or no? Mutation is there? Yes or no? Then only start the treatment. Otherwise, don't start. It can be leukemoid reaction. So, sometimes you can get confused. The blood picture is same as that of CML, but here hepatomegaly, splenomegaly, these all are absent. Got my point? And there is no bleeding disorder. Patient doesn't have any anemia. Other, other things are absent. It happens in response to infections, or sometimes in response to toxins, and rarely in certain malignancies. So, that is known as leukemoid reaction. You will say, "Ma'am, how I differentiate?" Being a doctor, for example, a patient is coming to me. The age of the patient is 50 years, and the patient is complaining that I'm having very frequent infections, okay? And I have done a CBC for certain disorder. I, I have done a CBC. In the CBC, I found the WBC count as nearly one lakh or 50,000. Huh? So, I can get confused. Ma'am, is it leukemoid reaction? So, I will not start the chemotherapy. Or is it CML? I will start. So, how should I differentiate? Based on the peripheral smear? Based on peripheral smear? How do you differentiate? So, listen. So, here the lab findings, it, it will never exceed one lakh. I told you, in leukemoid reaction, it will never exceed one lakh. And in CML, it is more than one lakh. Okay. See, see the differences here. Let me tell you, in leukemoid reaction versus CML, you get many questions here. Leukemoid reaction versus CML. In leukemoid reaction, the count is 25,000 to one lakh. Normal, it is 4,000 to 11,000. Never forget. In CML, it is more than one lakh, nearly two lakh, three lakh, like that. Here, you will get predominantly neutrophils, the mature neutrophils. Here, you will get all mature in stages. Here, you get only neutrophil. You, here you will get promyelocyte, myelocyte, metamyelocyte, band, along with neutrophil, not only neutrophil. Here, basically, you will get neutrophil. Okay. Here, NAP score is more. Here, NAP score is less because NAP score will highlight the neutrophil. I'm saying here, neutrophil is more, and I'm saying here, neutrophil is less. So, NAP score is something that differentiates the two, and you get many MCQs on NAP score. So, that is the significance of the NAP score. If you do the Philadelphia chromosome, obviously it's absent here. Here, there is no, no mutation. Philadelphia is always present. If you do the ABL-BCR fusion gene, it's absent here. It's present here. Got my point? Here, organ infiltration is absent. Here, also absent, but sometimes may be present. Spleenomegaly is absent here. It's present. I told you the reason for the spleen also. Got my point? How many of you got it? How many of you got it? We are done with CML. Finally, the treatment. I told you the treatment is imatinib. The most important therapy for CML is imatinib. And you can do for anemia, you can give the symptomatic treatment like blood transfusion. For thrombocytopenia, the symptomatic treatment is platelet transfusion. Before imatinib, we used to do bone marrow transplant, but nowadays, we don't do bone marrow transplant because imatinib is available. We hardly or barely do it. How many of you got it? How many of you got it? Huh? And finally, the prognostic factors. I'm coming on your doubts. Wait. So, finally, coming on the prognostic factors of CML. We have two index, Sokal index and Hasford index, to see the prognosis in them. The four, four things are common. Don't learn them. The fifth criteria is different. Here, we see the cytogenetics. Here, we see the basic. Basically, you don't get any much MCQs on the prognosis of CML, but you have to read it. The two types of the systems. We are done. How many of you got it? I'm done with CML. I taught you everything about CML. In a similarly way, we are going to cover AML and CLL, right? Now, the remaining three will be a little bit faster because you already have an idea now. This was the first one. It took time. I agree it took time, but it was worth giving the time because the remaining three will be really very fast. How many of you got it? Huh? So, the NAP or the LAP score. Okay. Listen. Tell me the precursors. Who is asking? Tell me the precursors. Someone is asking to repeat the NAP score or the LAP score. Say the full form. What is NAP score or LAP score? It is Neutrophil Alkaline Phosphatase, and Neutrophil is one of the leukocyte only. No. It's also known as Leukocyte Alkaline Phosphatase. So, basically, tell me the precursors. We have hematopoietic stem cell. It gives rise to myeloblast, promyelocyte, myelocyte, metamyelocyte, band form, and finally neutrophil. Let me draw these cells to explain. So, this is a cell of myeloblast. This is promyelocyte. Then myelocyte, then metamyelocyte, band form, a C-shaped, and finally neutrophil is multilobated like this. Now, let me draw the granules inside them. I'm interested in granules basically to explain you the NAP score. So, maximum granules are present in the neutrophil. A little bit in the band form. Very little in the meta, metamyelocyte, and hardly no granules here. Granules. So, NAP or LAP score is something. It is Neutrophil Alkaline. So, it is an alkaline phosphatase. Alkaline phosphatase is a component of granules. So, you tell me, which cell it will stain? It will stain this cell maximum. A little bit of this, a little bit of cell, and it will not stain these ones. Now, you tell me, what is happening in the leukemoid reaction? In leukemoid reaction, neutrophils are increasing in the blood up to one lakh, not more than that. So, LAP score will be high. What is happening in CML? In CML, these cells are increasing, not the neutrophils. So, their NAP score is less. So, in CML, the NAP score is less, and in leukemoid, it is more. Who was asking? Give me a thumbs up. You got it or you didn't get it? The concept should be crystal clear to you. Got it? I will cover all the topics. I will cover autocoids also. Okay. Okay, definitely I will cover the anti-cancer pharmacology also, Mohammad. Okay. What else? So, whatever topics you want now, write down in the chat. I'm having an eye there, and definitely I will schedule them one by one. Okay. So, there's a fixed schedule protocol in which we are going to schedule all these sessions one by one based on the demands of the student. So, the students who are demanding a topic more, we are ruling that prior, but definitely we are going to schedule all of them one by one. Everyone got it? Can we go ahead? Can we go ahead? Let's solve some MCQs on CML and come on the next leukemia. So, the first question is in front of you. Write down your answer in the chat box right now. Read the question and tell me the answer quick. Shall quick, tell me the answer. H. What causes this phenomenon? I already told you. I listen. So, this is the blood vessel. In the blood, normal count of WBC is 4,000 to 11,000. But in CML, instead of 4,000 to 11,000, it is two lakh. So, imagine two lakh WBCs are there. They all will move to the spleen. They will move to the spleen, and spleen will trap them because high cells are there, and spleen will enlarge. So, massive splenomegaly. This is the reason. I hope you got it. Read the question. Tell me the answer. A BCR-ABL hybrid gene is present in which leukemia? Obviously, the question is very easy. Is it Burkitt lymphoma, retinoblastoma, breast cancer, or CML? I guess the question is super simple. Of course, the answer is CML. So, I'm not waiting. I guess everyone. Yes, correct answer is D, and you all are right. You can see ABL-BCR fusion on the Philadelphia 22 chromosome. Read the next question. It's a clinical case. So, we will read it, understand it, and then come on the answer. Let's understand. There is a 60-year-old man. Age is always important, people. Age is always important. 60 years old. Okay. There is an old man presented with fatigue. Fatigue means patient has anemia. Weight loss. Weight loss means patient has hypermetabolism. And, uh, the hemoglobin is 10. So, of course, the patient is anemic. The WBC count is five lakh. Oh, come on. Five lakh. Normal is 11,000. It's five lakh. So, definitely it's a case of leukemia. Platelet count is four lakh, which is normal. 1.5 to 4 lakh is normal. Okay. Now, coming on the DLC. In the DLC, neutrophils are 55%. Lymphocytes are 4%. Monocytes are 2%. Basophils are 6%, which is more. But there is metamyelocyte, promyelocyte, and blasts. Normally, they are not present in blood. So, of course, it's a typical case of CML. And if it is CML, what is the correct answer? You can read the four mutations. Of course, in CML, the most important mutation, the only mutation is 9-22 translocation, that is Philadelphia chromosome. So, based on that, first make the diagnosis of CML, and based on that, come on the translocation. I hope you all are right. The correct answer is 9-22. This is a clinical scenario, and this is the approach for that. Okay. Now, coming on the next question. Easy question. Chromosomal translocation in CML. I guess everyone knows. Is it 2-8, 8-14, 9-22, or 15-7? What is the correct answer? Of course, the correct answer is 9-22. We have seen here 9-22. If I change from CML to AML, answer will become D. I will tell you in AML also, especially AML M3 type. I will come on that. Okay. Now, coming on the next question. A peripheral smear is having neutrophil. Neutrophil, we all have. There is nothing important in that. Basophil, we all have that. Eosinophil, we all have that. But we don't have myeloblast, promyelocyte, and band form in the peripheral smear. We have these cells in our bone marrow, but if you check my peripheral smear, I don't have it. Okay. So, if these are present in the blood, what does it mean? Is it mean AML, ALL, CML, or MDS? What does it mean? Of course, it is a garden party appearance. Multiple types of cells in peripheral smear. It is known as CML. The correct answer is C. And you all are right. You all are right. Absolutely right. Absolutely right. Okay. So, let's move ahead. CML is characterized by all accept. What do not happen in CML? Tell me. Leukocytosis? Yes or no. Leukemic? Yes or no. White blood cell increase? Yes. The WBC count is two lakh, three lakh, four lakh. Yes. Thrombocytopenia? Yes. The platelets will fall. This is also right. Splenomegaly? Yes. Splenomegaly also occurs. But is it increased LAP or increased NAP? No. No. No. No. No. LAP or NAP is decreased, not increased. Increased LAP or NAP occurs in leukemoid reaction, not in CML. So, correct answer here is C because it doesn't happen. They are asking except. You can see the LAP or the NAP score is something that differentiates the leukemoid reaction from CML. You have to learn that. Okay. You have to learn that. Tell me the next thing. The difference between leukemia and leukemoid reaction is done by what? I want to differentiate the CML from the leukemoid reaction. How to differentiate? Is it Leukocyte Alkaline Phosphatase? Is it immature cells? Is it total count, or is it ESR? Total WBC count is raised in both of them. ESR, we can't do ESR. Based on yes or we can. Immature cells, basically immature cells are more common in leukemia, but sometimes they present in leukemoid reaction also. So, the best to differentiate is the LAP score. LAP score is high in leukemoid reaction, and LAP score is low in CML. So, LAP scores are important. So, we are done with CML. I hope you know the definition, age, mutation, the three phases, clinical features, lab diagnosis, treatment, and prognosis of the CML. Can I skip and come on the next one? AML. Can I start the AML? Give me a thumbs up. Are you full of energy still? Huh? Can we continue the next leukemias with the same energy, with the same enthusiasm? Yes. Give me a thumbs up. Let's start AML. So, coming on the next one, AML. Acute Myeloid Leukemia. AML. So, what is happening here? Listen, listen. People come here. The first thing, look at the age. The CML was occurring after 50 years. Usually, exceptions are always there. AML usually occurs 15 to 40 years. Not in old age. AML do not occur in old age usually. But exceptions are there. I told you, exceptions are there. Okay. Got it. So, here usually we get the AML between 15 to 40 years. Now, see that what is the difference in pathogenesis? Everyone on the screen. What was happening in CML? Same in CML, these five cells have the mutation. Which mutation? It was 9-22 translocation. Because of which these five were moving in the blood. So, in the blood, we were having all five: myeloblast, promyelocyte, myelocyte, metamyelocyte, and band, including myeloblast also. But all five are there. And the neutrophil, eosinophil, basophil, monocyte, they all are there. They all are present here. Got it? Say yes or no. So, they all are present in the blood. That is garden party appearance. Okay. That was CML. What is happening in AML? Mutation occurs only, only in myeloblast. That's it. That's it. None other cell. Which mutation? I will tell you. Mutation will be different. There are different types of AML in which different types of mutations are there. Here, the translocation is 15-17. Either 15-17 or translocation between 8-21, not 9-22, or there is inversion 16. The 16, there is a gene in the 16 which get splitted and inverted. So, inversion 16, inversion 16. So, either 15-17, 8-21, or inversion 16, one of the mutation usually occurs here, only in myeloblast. So, in the blood, only myeloblast is coming, not others. Only myeloblast is coming. So, school uniform appearance. That is AML. How many of you got it? How many of you got it? Say yes if you got it. H. So, in AML, only myeloblast is mutated, and that is doing uncontrolled mitosis. So, that is spilling the marrow completely and spilled over in the blood. So, here, if you take the blood sample and make a smear, in the smear, you will get only one type of cell, that is myeloblast. There are eight types of AML based on FAB classification. We don't have FAB classification for CML. In the CML, we were having three phases: chronic phase, accelerated phase, and blast phase. If you remember, here we don't have phases. We have FAB classification. The French, American, British classification. Based on which there are eight types, including M0. So, M0, M1, M2, M3, M4, M5, M6, M7. There are eight types of AML. You have to learn their names. Sometimes you will get the names in the options. So, you don't recognize, is it M1, M2, M3? So, you have to understand that M0 is minimally differentiated AML. Minimally differentiated AML. M1 is AML without maturation. M2 is AML with maturation. Learn these three. Minimally differentiated, without maturation, with maturation. Now, after that, I'm having a way to learn that. M3 is promyelocytic leukemia. Promyelocytic. This is myeloid. Just a second. This is learned as PM. Promyelocytic. This is myeloid monocytic, and this is monocytic. This is erythroid, and this is megakaryocytic. Let me tell, let me tell you. So, we are having totally eight types. M0, M1, M2, M3, M4, M5, M6, and M7. How to learn that? So, AML with minimal differentiation. Minimal differentiation, without maturation, with maturation. We have learned this. Okay. Now, how to learn? M3 is promyelocytic acute promyelocytic leukemia. M4 is myeloid monocytic. This was promyelocytic. This is myeloid monocytic. Acute myeloid monocytic leukemia. M5 is monocytic only, monocytic. So, acute monocytic leukemia. Then M6 is erythroid. Acute leukemia. And M7 is megakaryocytic. So, acute megakaryocytic leukemia. How many of you got it? So, you can read the word promyelocytic, myeloid monocytic, monocytic, erythroid, and megakaryocytic leukemia. Acute in leukemia, you can add anytime. Say yes. Out of which, there is a special type that is M3. In M3, there is always DIC, disseminated intravascular coagulation, DIC is there. Okay. So, I will tell you the special, special points in all seven, all eight, one by one. All of them are MPO positive. MPO is a special stain. I will tell you what is MPO, but here this one is MPO negative. Only this one is MPO negative. Rest all are MPO positive. What is MPO? I will tell you later. It is, it is a type of special stain. Okay. Myeloperoxidase. Myeloperoxidase stain is there. Okay. M1, nothing important. M2, in M2, there is 8-21 translocation and maximum chances of chloroma. I will tell you what is chloroma. Okay. In M3, 15-17 translocation is there, and maximum Auer rods are seen in M3, and in M3, DIC is also there. In M4, inversion 16 translocation is there. In M5, 9-11 translocation is there. So, something, something special in each of them. Out of them, the least common type is M7, and the most common type is M2. So, you have to learn these special points. Most common type is M2, and least common type and the worst prognosis of all is M7. M7 is the worst one. Okay. And it is present in Down syndrome, the M7. So, you get simple, simple MCQs on that.

Now, what are the clinical features? Of course, in all leukemias, all leukemias, these three clinical features are common. Now, here, the myeloblast is doing uncontrolled mitosis. So, it replaces RBCs. RBCs are not formed. It replaces platelets. Platelets are not formed. So, since RBCs are not formed, patient has anemia. Since platelets are not formed, patient has bleeding disorders or thrombocytopenia. And since myeloblasts are present in the blood, you know, the mature forms are not coming, only myeloblasts are coming in the blood, that's why patient has high propensity of infection also. So, these are the clinical features. You will see, "Ma'am, this is common as of CML." In CML also, we have this. Okay, I got it. But there is one additional feature which was not present in CML. Everyone here, listen. Let me tell you one difference between CML and AML. You tell me, what is the difference? What was happening in CML? Please understand what was happening in CML. All these five cells were doing uncontrolled mitosis because of 9-22 translocation, and they were shifted in the blood, and after coming in the blood, these all five, they remain in the blood only. They remain in the blood only. They don't go anywhere else. Organ infiltration is not there in CML. Now, please understand what is happening in AML. Please understand here what is happening in AML. In AML, only myeloblast is doing uncontrolled mitosis, and only myeloblast is coming in the blood. Others are not coming. Okay. It's school uniform appearance. And after coming in the blood, it infiltrates in various solid organs and producing lymphoma. So, lymphoma is a feature of AML. It's a feature of AML, but not CML. How many of you got this point? How many of you got this point? Organ infiltration. It is known as organ infiltration. So, organ infiltration occurs in AML. Myeloblast do so, but in CML, it doesn't occur. It never occurs. Say yes if you got it. How many of you got it? Huh? Got my point? So, in which organ it is infiltrating? Enumerate them. It can infiltrate in the bone. So, patient has bone pain. It can infiltrate in the lymph node. Patient has lymph node lymphadenopathy. Lymph nodes are enlarged. It can infiltrate in the spleen. Splenomegaly. In the liver, hepatomegaly. In the kidney, kidney infiltrates are there. It can infiltrate in the gums also. Can you see gum hypertrophy? The blasts, myeloblasts from the blood, they are moving in the gum, and this producing the gum hypertrophy, which is very peculiar. It is seen in M4 and M5. M4 and M5, you get the MCQ on that, not in others. M4 and M5. And it can move in the orbit and it can swell the eyeball orbit, orbit. Okay. It is known as chloroma. It is known as chloroma in the eyeball. It is known as chloroma, and it happens in M2. So, chloroma happens in M2, and the gum. Chloroma in the M2, and this one in M4, M5. M4, M5. M2, M4, M5. M2, M4, M5. In the orbit, it's chloroma. Here, it's M2. And in the gum, it's M4, M5. How many of you got it? Say yes. So, this is the organ infiltration which is not a feature of CML but a feature of AML.

Coming on the lab diagnosis quickly. In the lab diagnosis, of course, in the blood, hemoglobin is less, platelets are less, and WBCs will be more. Of course, hemoglobin will be less, platelets will be less, WBCs will be more. It is more than one lakh. But only one type of cell. In CML, we got these five types of cells in the blood. No, not here. Here, we get only one type of cell, which one? Myeloblast. That's only one cell, myeloblast. So, only myeloblast is coming in the blood. And 99% of the cells in the blood are myeloblast. It is spilled over because of the because there are mutations here, either 15-17 mutation or 8-21 mutation or inversion 16 mutation, because of which it is doing uncontrolled mitosis, and it is spilled in the blood. So, you will get only one type of cell, myeloblast. Can you see only one type of cell? Now, see this picture. Which, how many types of cells I get? Only one type of cell. These all cells are myeloblast. You can see all the cells shown in this image. They all are myeloblast with not garden party appearance. You will see it's a school uniform appearance. The, in a school uniform, everyone is in the same dress. So, you can see, uh, in the cytoplasm, the red color rods are present in the cytoplasm. These are Auer rods. Based on the Auer rods, if you are attending my lecture from the beginning, you understand. I can identify this is myeloblast, not lymphoblast, because Auer rods are present. So, Auer rod is the feature that differentiate the myeloblast from the lymphoblast. Yes, Auer rod is the feature. Okay. Here, Auer rods are present. Maximum Auer rods are present in M3. Now, you can understand all those. Maximum Auer rods are present in M3. It is present in M3. Maximum Auer rods. So, it is not present in all myeloblasts. You can see out of the seven, eight cells shown to you, only three of them have Auer rods. This one, this one, and this one. Others do not have. So, a myeloblast. This is a myeloblast. This is the nucleus of the myeloblast. A myeloblast which is having Auer rods in the cytoplasm. Such a myeloblast is known as a Auer cell. What is an Auer cell? It's a myeloblast with Auer rod. So, maximum Auer cells are present in M3, or maximum Auer rod cells are present in M3. It's a question. It's an MCQ. Please learn that. Got it? So, out of the four, two you can understand. Now, I want you to compare the AML with CML. Compare these two, then we will come on the leukemoid. First, see the myeloid. So, we are done with the leukemias, by the way. So, please, can you compare? Now, say, "Ma'am, here in AML, only myeloblasts are present in the blood." I can see only one cell. And in CML, I can get myeloblast, but along with myeloblast, I get promyelocyte, myelocyte, metamyelocyte, band form, neutrophil, eosinophil, basophil, monocyte, everything. So, here it's a garden party appearance, and here it's a school uniform appearance. You can compare. Don't mug up. I want you to have a look on this peripheral smear and on this peripheral smear, see how many types of cells you can see here, and see only one type of cell here, that too with the Auer rods. So, if the peripheral smear is provided to you in your exam, can you identify which type of leukemia is it? Say yes if you got it. Say yes. Huh? What's the purpose of M1, M2, M3? Uh, Cover Sura. So, at your level, if you're doing MBBS now, so learning the classification is only important, but the prognosis of all of them is different. The mutation of all of them is different. The treatment of all of them is different. So, if you are doing your MD in hematology or in pathology, then understanding the various types with their prognosis, with their treatment formulas will be important for you. But now, at your level, generalized learning the classification is more than sufficient. But these are different eight types having different treatment and different prognosis. Got it? Got my point? So, treatment will be different, prognosis. That is the only answer. Can we go ahead? H. Yes, got it. So, we have seen the blood picture. Now, coming on the bone marrow. Of course, cellularity is more in the bone marrow. You can see hyperscellular because myeloblasts are doing uncontrolled mitosis and replacing everyone. So, here most of the cells are myeloblasts. Myeloblasts are more than 20%. Usually, it is less than 5%. Here, more than 20%, and they have Auer rods in them. They are cells. Erythroids are less, and megakaryocytes are less. So, obviously, we can understand. Okay. Obviously, we can understand.

Now, cytogenetics. You will get the three types of mutation. In M2, it's 8-21 translocation. In M3, it's 15-17. And in M4, it's inversion 16. But in others, there are other translocations. Don't learn them. Usually, you get questions on these. Just a second. Give me a minute. Just a second. Give me a minute. Let me share it again. Okay. I guess you can see. Okay. So, please learn that in M_sub_2, in M3, and in M4. So, in M2, it's 8-21. In M3, it's 15-17. In M4, it's inversion 16, on which you get the question. In cytochemistry, listen. I am teaching you four types of leukemia. This is the second one. We have already completed CML. Yes or no? We have already completed CML. Yes. Now, after that, I am covering right now AML. After that, I will come on ALL also. Okay. And finally, I will come on CLL. So, basically, the cytochemistry, the special stains are important here. Here, here, here, we don't have any special stain. Okay. So, here in CML, I told you only one special stain to learn: NAP or LAP score. NAP or LAP score, and that too is falling in CML. This is required to differentiate the CML from leukemoid reaction. We have seen that. Now, basically, the real confusion occurs here and here and here also. School uniform appearance. Here also school uniform appearance. Here, in the blood, you get only one cell, myeloblast. Here, in the cell, you get only one cell, that is lymphoblast. Here, the mutation occurs in myeloblast that is doing uncontrolled mitosis and spilled in the blood. Here, the mutation occurs in the lymphoblast doing uncontrolled mitosis and spilled in the blood. The only way to differentiate them is Auer rod. Here, Auer rod is present. Here, Auer rod is absent. But sometimes, we cannot appreciate the Auer rod, and we really get confused that which type of leukemia is there. So, clinically, both of them are same. Okay. This is also acute. This is also acute. Acute has bad, poor prognosis. How many of you get it? So, here, really, we want the, uh, cytochemistry. So, I will tell you total five stains. Three of them are positive here, but negative there, and two of them are positive here, but negative there. So, learn the total five together at one shot, at one place, at one shot, to differentiate the two acute leukemias from each other. Okay. So, these are the five special stains. Out of the five, MPO, Sudan Black, and NSE is positive in AML, but PAS and acid phosphatase is negative here in AML. PAS and acid phosphatase is positive in ALL, but not in AML. You are getting my point. You're getting my point. So, the three, so you can compare the AML with ALL in the same table. I will show you in the next leukemia when currently I'm teaching you AML. After this, I will teach you ALL. So, cytochemistry, I'm teaching you in common for both of them. So, learn the five stains. MPO, myeloperoxidase, it is positive here. There are eight types. It is negative in M0, and except M0, it is positive everywhere from M1 to M7. But it is negative in

M0 and here it is always negative. Always negative. Sudan Black, it is positive in AML, but it is negative in ALL. NSE is nonspecific. Please learn NSE. It is also positive only in M3, M4, M5, not everywhere. Only in M3, M4, M5, but it is always negative here. The PAS, periodic acid Schiff, it is positive there. And acid phosphatase is also positive there. So, these are the two which are positive there, and these are the three which are positive here. How many of you got it? So, M0, Sudan Black, NSE, PAS, acid phosphatase positives. So, learn them in a sequence. And learn AML, ALL. I want you to learn these three are positive here but negative here, and these two are positive here, negative here. This is the generalized thing. But here, NSE is positive everywhere except M0. You have to learn that. And NSE is positive only in M3, M4, M5, not everywhere. M3, M4, M5. Yes. So, how many of you got it? Give me a thumbs up. Give me a thumbs up. You got it. So, please learn that.

So, can we go ahead? Can we go ahead? So, that is the cytochemistry. Others not important. We are done with that. And the treatment here, we don't have any targeted therapy. Unfortunately, we have targeted therapy for CML. The CML targeted therapy is imatinib. Here, we have to perform bone marrow transplant if a donor is available. If the age of the patient is young, donor is available, HLA matching is there, and everything is suitable, the best is to go with the bone marrow transplant. If bone marrow transplant is not possible, we will give chemotherapy. We don't have targeted therapy. Which chemotherapy? We use three drugs. We use cytosine arabinoside, anthracycline, and 6-thioguanine. We use these three. The combination of these three chemotherapy. We don't have targeted therapy. This we will give everywhere except M3. In M3, we give retinoic acid, teniposide as a treatment because in M3, we have DIC. In M3, we have DIC. Please learn M3 is a special type. What are the eight types I told you? M0, M1, M2, M3, M4, M5, M6, M7. Can you tell me the important features of all of them? M0, learn it is M0 negative. Rest all are M0 positive. M1, M2, nothing important. Nothing important. M3, DIC, it is unique, having DIC here. Maximum cells, cells, maximum Auer rods, maximum Auer rods, maximum cells. Okay. And in M2, chloromas are there. In M2, chloromas. You know what is chloroma? It gets swelled. Chloromas are there. And in M4, gum infiltration is there. Gum infiltration is there. These are the important points you have to learn. I've told you already, we are revising. And in M3, M4, M5, NSE is positive. That's it. So, please learn it. It is already given in the notes. Please learn that. These are the important points. The most important is DIC. So, for that, the treatment of all of them is same. We give chemotherapy. You know the three chemotherapy drugs. But treatment of M3 is different. We don't give chemotherapy here. We give retinoic acid or teniposide here. Got it? So, please learn.

Now, coming lastly on the prognostic factors. You get many questions on the prognosis of AML. Please learn that. So, learn the good prognostic factors and bad prognostic factors. Most important is the age. If the age is less than 40, prognosis is good. If age is extremes, either less than two or more than 50-55, the prognosis is poor. So, extremes are poor. The middle age is good, but extremes are poor. M2, M3, M4 is good, but except that M0, M6, M7 are poor. Okay. M1 is moderate, you can say. Okay. So, M2, M3, M4 are good. You have to learn that. Blast with Auer rod, this is the karyotype is good. But complex karyotype is bad. If total leukocyte is less than 2.5 lakh, it's good. If it is more than, you know, less than, I'm sorry, 25,000 is good. If more than one lakh, it's bad. 15-17, 8-21, and inversion 16 is good. But apart from that, deletion of 5, deletion of 7 is bad. These three that which we have learned, these are the good. So, you have to learn the good and the bad prognostic factors. We will solve some MCQs and we are done with AML also. So, out of the four, who are done? How many of you got it? Read it. All of the following are poor prognostic factors except which of the following is not a poor prognostic factor in AML? Is it inversion 16 good or bad? I guess this one is good. This one is good. Complex karyotype, it's bad. M7, it's bad. And deletion of 7q, it's bad. So, only one is good, that is inversion 16. Rather than don't judge, don't guess. I mean, have a look on this table and then tell me. So, you can see inversion 16 is coming on this side, but the remaining three are coming on that side. You can see complex karyotype, you can see M7 type, and you can see deletion of 7q. They are the bad ones. So, basically, you have to learn the prognostic factors. Please, I'm insisting. Please. Yes, you all are right. Absolutely right. Okay.

The next one. AML with gum infiltration, hepatosplenomegaly, most likely to be. So, gum infiltration occurs in which one? I told you gum infiltration. Chloromas are there in M2, but gum infiltration occurs in M4 and M5. Out of M4 and M5, only M4 is given in the option. So, go with M4. If M5 is also given in the option, that's also correct. So, gum infiltration occurs in M4, M5. If I change the word gum infiltration with chloroma, chloroma is the eye, eyeball, the orbit involvement, then the answer will become M2. In the same question, the answer will become M2. How many of you got it? WHO classification is not important here. FAB classification is important. Prove it with the question that comes on the FAB classification. Okay. AML with worse prognosis. Tell me, poor prognostic factor. Bad prognostic factor. 8-21 translocation. This is good one. Inversion 16. This is also good one. Normal cytogenetics is good one. Not the complex one. But monosomy 7, 7q, it's a bad one. So, the answer is this one. You can see monosomy 7 is poor. But you can see, you can see 8-21 is good one. Here you can see 8-21, inversion 16 is also good one. But the 7q is bad one. So, you have to learn this table. Got my point? Got my point. One more question for you. Translocation characteristic in acute promyelocytic leukemia. You first tell me, acute promyelocytic leukemia is what? Is it M0, M1, M2? I have told you the classification. M0, M1, M2, M3 onwards. I told you how to learn M3, M4, M5, M6, and M7. How to learn that? I told you a trick to learn. What is the trick? Acute promyelocytic leukemia, myelocytic, myelomonocytic, erythrocytic, and megakaryocytic. So, they are asking promyelocytic. The promyelocytic is M3. So, basically, they are asking the translocation in M3. So, I asked you, I told you to learn the translocation in M2. The translocation is 8-21. In M3, it's 15-17. And in M4, it's inversion 16. Currently, they are asking in M3. So, my answer is 15-17. Currently, they are asking in M3. So, it is a two-step question. First, reading the question, you have to see acute promyelocytic leukemia is M3. And what is the mutation in M3? It's 15-17. So, answer is 15-17. If in the same question, it is 15-17 and M3. How many of you got it? If I ask you M2, then answer will become 8-21. And if I ask you in M4, answer will become inversion 16. So, basically, you have to learn it separately. Auer rods are seen in lymphoblast or myeloblast. Lymphoblast or myeloblast, not in blast. Myeloblast, obviously. So, obviously, the Auer rods are seen in, I guess everyone knows, it's myeloblast. This is the way to differentiate. How we differentiate myeloblast from the lymphoblast? You can see in the myeloblast, we have Auer rods here, but in lymphoblast, we don't have Auer rods. These all are your previous year questions of different exams. You can see occurs in which one? We know DIC occurs in M3. But what is the name of M3? What is M3? Is it acute myelocytic leukemia or acute myelomonocytic? This one is M3. This one is M4. This is CML. And this is autoimmune leukemia. They are out of stock and we don't consider them as differential, although. So, correct answer is M3. So, correct answer is A. I guess you all are right. So, this is a way we approach. This is a way we approach. Okay.

One more image-based question is there. There is a 16-year-old leukemia patient who is having decreased platelet. Look at the age. Look at the age is always important. Platelet is less. Okay. Prolonged PT and APTT, I mean bleeding time is more. So, thrombocytopenia and peripheral smear is given. So, combine the clues. Look at the age. Look at the image and look at the thrombocytopenia. So, combine all three and tell me the translocation. Tell me the combined translocation. So, here you can see maximum, all these cells are same. They are not different. So, it is school uniform appearance. Then in the cytoplasm, I can see the granules, I mean, these rod-like materials. This is Auer rod. Although image is not very good, but here you can see the Auer rods. Appreciate the Auer rods. So, appreciate the Auer rods. The cell is full of Auer rods. So, basically, these are Auer rod cells and maximum Auer rod cells, they all are Auer rod cells. Maximum Auer rod cells are seen in M3, and the mutation in M3 is again 15-17. So, it's an indirect question. First, based on the question, clinical history, and based on the image, come on the diagnosis. It is a leukemia with maximum Auer rods. Maximum Auer rods occur in M3, and the mutation in M3 is 15-17. That's why the answer is 15-17. How many of you got it? Got it. The next question. Maximum Auer rods are seen in. The answer is M3. I told you many times. Okay. So, it's the same question. Yeah. Non-specific esterase is positive in all AML except. NSE is positive only in three AMLs. In these three, M3, M4, and M5. I told you it is positive in M3, M4, M5, but not in M6. So, correct answer is M6 because they are asking except. So, correct answer is M6. Got it? So, it's positive in M3, M4, M5. You can see, but not in M6. Okay. Got it. So, we are done with that. I guess many questions we have covered. We are done with AML, CML, and AML. Let's start the next one. ALL. Can I start? How many of you are ready? Can we start? How many of you are with full energy yet? Still in energy. Can we continue? Can we continue the next one? Say yes. Definitely, I will consider Muhammad. Definitely, I will cover all these topics. You can text it here. One by one, I will schedule it. Okay.

So, let's come on the next topic that is ALL, the third leukemia. We have covered this, covered this. Now we will cover this and finally this one, and we will have a comparative table of all four. So, let's come on ALL. So, what is happening in ALL? Now, in ALL, what will happen? Listen, let's listen. Till now, we have covered two. Now, so let me revise you what happened in CML, AML, and then come on ALL. In CML, TCT. In CML, all these five cells were mutated. The name of the mutation is 9-22 translocation, and they all five were moving in the blood. That is CML. Okay. We have already seen that in AML, only myeloblast was mutated. We know the three types of mutation. It's 8-21, it was 15-17 translocation, and it was inversion 16. Because of which, only myeloblast was coming in the blood, and that was known as AML. Okay. Now, we are coming on ALL. In ALL, the mutation occurs in lymphoblast. So, only lymphoblast will come in the blood. Only lymphoblast will come in the blood, not others. Only lymphoblast will come in the blood. So, that is ALL. So, that is ALL. How many of you got it? So, because lymphocytes are of two types, B lymphocytes and T lymphocytes, so that's why ALL is of two types, pre-B cell ALL or T cell ALL. They occur in children. See the age group. They typically occur in children. So, you know the age group here. Age group, I told you more than 50 years. Here I told you 15 to 40 years. And here I'm telling you in children. If it is pre-B cell, it occurs 3 to 5 years. And if it is pre-T cell, it occurs in adolescents. But both of them are children. They are toddlers or they are children. So, basically, it's a leukemia of children. So, basically, if you're getting a question, there is a child or in this age group and having leukemia, only one option is there, that is ALL. So, please look at the age and compare the age of all of them. So, it occurs in children. Here, only lymphoblast is coming. So, in the pathogenesis, here I told you, here all five are coming: myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form. These five are coming in the blood. Here, only myeloblast is coming. Here, only lymphoblast is coming in the blood. So, this is garden party appearance. This is school uniform with Auer rod. This is school uniform without Auer rod. That's it. It is as simple as that. I hope you all are learning it. Say yes if you got it. Huh? SLTB. I will cover it all. Don't worry. One by one. Okay. First, understand the leukemias here. Okay.

Tell me the pathogenesis. Tell me the mutation in pre-B cell. The mutation is hyperploidy. Most commonly hyperploidy or hypoploidy. Either the chromosome increases in number, more than 46 chromosomes, or decreases in number, less than 46. So, hyperploidy or hypoploidy can be there. Loss of mutations can be there. And one of the mutation is 9-22. You say, what 9-22? But 9-22 fusion, ABL-BCR fusion, we have seen in CML. You are teaching us ALL. I taught you this one is in CML. So, in CML as well as ALL, in both of them, 9-22 translocation occurs. So, here also, fusion formed ABL-BCR. Here also, ABL-BCR fusion formed. I am telling you in the pathogenesis, here also we have 9-22 translocation. So, fusion gene is formed. Here also, 9-22 translocation, fusion gene is formed. So, here ABL-BCR fusion gene, the size is 210 kilodaltons. And here, the ABL-BCR fusion gene, you know how it is formed? The same way it is formed. The transfer, the exchange takes place. But here, the size of the fusion gene is only 190 kilodaltons. So, that is the, you know, someone was asking now, 210 and 190 kilodaltons. So, we have to see the size. Based on the size, we can identify the fusion gene size. Here also, ABL-BCR fusion gene. Here also, fusion gene. But based on the size, we can identify is it CML or is it ALL. How many of you got it? Although this is the only mutation which occurs here. Here it is one of the minor mutation. The major mutation is hyperploidy or hypoploidy. It is one of the minor. But in CML, it is the only mutation. Give me a thumbs up, people. Please interact. Please say, give me a "yes" that I'm teaching you live. Say yes if you got it. Say yes. And in T cell, the mutation is not gene. The mutation occurs on the NOTCH gene. So, what are the mutations here? Either hyperploidy or hypoploidy or 9-22 or NOTCH gene. These are the mutations here. And based on the size of the fusion gene, we can differentiate is it CML or is it ALL. So, we can differentiate according to FAB classification. AML was of eight types, M0 to M7. But based on FAB classification, ALL is only of three types. There is no L0. We directly have L1, L2, L3. We have only three types. We don't have L0. We have only three types. L1, L2, L3. You can see L1, L2, L3. L1 is most common, having best prognosis. L3 is rare and having worse prognosis. You can see this is a rare, worst prognosis. Okay. So, that is L1, L2, L3.

Now, here you can see, here you can see the bone marrow failure features here also. Here, only cell is lymphoblast. The mutation occurs in the lymphoblast. Which mutation I told you? Various mutations, either hyperploidy or hypoploidy or 9-22 translocation or NOTCH gene mutations. Because of any mutation, this becomes cancer cell. It keeps on doing mitosis, uncontrolled mitosis, mitosis, mitosis. It will replace everything else. So, no RBCs are formed, patient have anemia. No platelets are formed, patient have bleeding manifestations. Although the lymphoblasts are many. So, WBC count will be more, but they are the immature cells. So, patient is highly prone to infection. So, these are the three features which are common for all leukemias. How many of you got it? But here, along with the leukemia features, patient have, you know, organ infiltration. So, organ infiltration occurs in AML also, in ALL also. But the organs will be, you know, some unique organs are there. Here, in ALL also, organ infiltration is there. So, here the lymphoblasts are coming in the blood. First, in the marrow, these lymphoblasts replace everything else. Okay. Then it is spilled in the blood. After coming in the blood, it will move in various organs. Which organ? Enumerate them. It can go in the bone. It can go in the lymph node. It can go in the spleen. It can go in the liver. It can go in the mediastinal lymph nodes. It can go in the meninges, and it can go in the testes in the boy, in the male, I mean. So, these three things are unique which are present in ALL but not in AML. And these are common in both. These are common in both. And gum infiltration and chloroma was unique there. You're getting my point. So, I'm telling you AML, I'm telling you ALL. Okay. I taught you here, only myeloblast will do the uncontrolled mitosis and spill in the blood. And after coming in the blood, the myeloblast will move in various organs. Here, the lymphoblast will do the uncontrolled mitosis. From the bone marrow, it is spilled in the blood. And from the blood, it will go in various organs. So, that is the two types of leukemia as we are comparing. Okay. Here I told you, in both of them, liver infiltration is there. Hepatosplenomegaly is in both of them. Lymph node infiltration, lymphadenopathy is in both of them. Kidney infiltration in both of them. Okay. So, these are the common bone infiltration in both of them. It is common. But there is something unique organs here. Some unique organs here. So, here the unique organ is gum infiltration and chloroma. Chloroma is the orbit. So, orbit, that is chloroma, and gum infiltration is unique here. Orbit infiltration is seen in M2, and gum infiltration seen in M4 and M5. I told you here the unique is mediastinal lymph nodes, meninges, meninges, and testes. Testes, that is not there. But these organs are common which are infiltrated in both of them. But in CML, there is no infiltration. There is no organ infiltration. I hope you are getting. Say yes. Say no. Akai, I hope you have joined late. I have already taught you the NAP score there. Okay. So, you can go back in the session where I have taught you the differential diagnosis of CML. There I have taught you the NAP score in detail, in much detail. Okay.

So, coming on the lab diagnosis of ALL. Currently, I'm teaching you ALL. Okay. So, ALL, you can see the blood picture. The hemoglobin is less. The platelet is less. Obviously, in the blood, you get only one cell, only one cell, only one cell, which cell? It's lymphoblast. You can see all cells, school uniform appearance. All the cells are same. School uniform appearance. They all are lymphoblast. All the cells are same. They are lymphoblast. We are done with this one. We are done with this one. We are done with this one. Compare, people. Compare. Open your eyes and compare them. See here, we get only one cell, myeloblast. Here, we get only one cell, lymphoblast. So, this is also school uniform appearance. This is also school uniform appearance. But here, we are getting the Auer rods in the cytoplasm, people. And here, there is no rod. These are myeloblast. These are lymphoblast. And here, we are getting five types of cells. We are getting myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form. Neutrophil, eosinophil, basophil, monocyte. It is a garden party appearance. A beautiful garden party where everyone is in different beautiful dresses. How many of you got it, people? Now, if the peripheral smear is provided to you, will you be able to identify the type of leukemia? Until now, the last one is Pandic, that I will teach you now. Then we will do the comparison of all four at one place, in one shot. Say yes. So, that is lymphoblast. Here, we are getting only lymphoblast. See, this image can also compare one type of cell. All the cells are same. It's only one type. It's not garden party, school uniform. So, it's school uniform. Is it with Auer rod or without Auer rod? None of the cell have Auer rod. So, they all are lymphoblast. Okay. So, you can get any cells. So, they all are lymphoblast. All of them are lymphoblast. All of them are lymphoblast. You can compare. Now, we are done with this. Coming on the bone marrow. Again, the cellularity is more. But this time, the leukemic cells are lymphoid, not myeloid. This time, the blast is lymphoblast. RBCs are less. WBCs are less. Obviously, in the cytogenetics, we have already seen that you can get hyperploidy, hypoploidy, 9-22, NOTCH. So, in the cytogenetics, you will get the exact mutation. And cytochemistry also, I taught you. In the cytochemistry also, I taught you. You have to compare the five stains to differentiate the myeloblast from lymphoblast. Okay. Now, you can get confused sometimes. You can see, ma'am, this is also school uniform appearance. Listen, listen. And this is also school uniform. What if I miss this Auer rod? You are saying only Auer rod is the difference. If I miss this rod, what I will make wrong diagnosis? I will give wrong treatment. I cannot do that. So, use five special stains. What are the five special stains? These are these myeloblast. You can see all these school uniform cells, myeloblast. They are M0 positive, they are Sudan Black positive, and they are NSE positive. But they are PAS negative and acid phosphatase negative. These are PAS positive and acid phosphatase positive. So, you can see the cytochemistry is absolutely different. So, lymphoblasts are PAS and acid phosphatase positive. And myeloblasts are M0, Sudan Black, and NSE positive. So, cytochemistry may you have to perform all five together so that crystal clear diagnosis. So, you have to perform all five together. You can see here. So, AML, ALL. Currently, I want ALL. So, in ALL, these two are positive. You can see which two? PAS and acid phosphatase positive. These are positive here. And these are negative in AML. Rather, in AML, these three are positive: M0, Sudan Black, and NSE, which are negative here. So, based on this, we can do the diagnosis. Say yes. Got it? Yes. So, that is the diagnosis.

Treatment again. We don't have any targeted therapy. In CML, we have targeted. But here, we don't have targeted. So, we do bone marrow transplant, the best treatment, if the donor is available. Actually, matching is done. Otherwise, chemotherapy is the option. In the chemotherapy, but the chemotherapy drugs are different there. In AML, we have seen the chemotherapy drugs as thioguanine. We have seen cytosine arabinoside. Here, we have vincristine, prednisolone, asparaginase, daunorubicin, and adriamycin, and L-asparaginase. So, these are the chemotherapy drugs we give here. And we give the symptomatic treatment for anemia, we give blood transfusion. For thrombocytopenia, we give platelet transfusion. That is a symptomatic treatment, that is not cure. Okay. Got it. Prognostic factors. Finally, the prognostic factors. We have good prognosis. We have bad prognostic factors. 2 to 10 years, it occurs in children. I'm teaching you ALL. I'm teaching you ALL. It occurs in children, 2 to 10 years age group is good. But extremes are bad. Less than two, more than 10, both extremes are bad. The same was there in AML. Okay. Here also, extremes are bad. In females, female child, the prognosis is good. In male child, the prognosis is bad. In whites, the prognosis is good. But in blacks, the prognosis is bad. It's genetically okay. If the CNS involvement, meningeal involvement, mediastinal lymph node involvement, testicular involvement is there, prognosis is, um, if involvement is there, if no involvement, prognosis is good. But if the involvement is there, obviously the prognosis is bad. Okay. Hyperploidy is good. Hypoploidy is bad. Please learn that. Please learn that. Okay. 9-22 here is bad. Okay. So, please learn the important prognostic factors. We will solve certain MCQs and move on the last leukemia that is CLL, quickly. Okay.

So, coming on some MCQs. What is the poor prognostic indicator of ALL? Huh? Female gender is good. If the WBC count is less than 50,000, it's good. Okay. Age more than 1 to 10 is good. Okay. Less than one, more than 10 is bad. But hyperploidy is bad. Hyperploidy is good. Hyperploidy is bad. You can see hyperploidy is good. Hyperploidy is bad. So, you can see hyperploidy is bad. Remaining three are good. So, you have to learn the prognostic factors of all of them. Okay. Got it. So, PAS, periodic acid Schiff. PAS stain. PAS stain shows block positivity in which? Is it show block positivity in myeloblast or lymphoblast or monoblast or myelomonoblast? So, PAS is used to differentiate myeloblast and lymphoblast. In myeloblast, it's negative. In lymphoblast, it's positive. Lymphoblast. So, you see PAS is one of the stain that is differentiating the two. And acid phosphatase. These are the two stains which are positive in lymphoblast, but not in myeloblast. Instead of PAS, if the question is on acid phosphatase, so PAS and acid phosphatase both of them are positive in lymphoblast. But the M0, Sudan Black, and NSE are positive in myeloblast, not lymphoblast. Okay. So, that is the thing. One more question on the prognostic factor. We can skip now. Read the next question. See the age, 12 male. Age is important. Gender is important. See, 12-year-old. So, we are talking about a child. Okay. A male child having fatigue, fatigue means anemia. So, imagine a 12-year-old child having anemia. On physical examination, there is palpable axillary and inguinal lymphadenopathy. So, the lymph nodes are enlarged. Various lymph nodes are enlarged. The spleen is also palpable. So, patient have splenomegaly, patient have lymphadenopathy, and peripheral smear is given to you. In the peripheral smear, I can see all the cells are looking same, school uniform appearance. Garden party. Now, try to search the Auer rod in any of them. Do you find the Auer rod? No. We are finding hardly any cytoplasm. Hardly any cytoplasm. Most of them, they don't have any cytoplasm. They are lymphoblast. So, is the option ALL or CLL or infectious mononucleosis or iron deficiency anemia? Of course, it's leukemia. So, which leukemia is it? ALL. Huh? Looking at the age and looking at the image, my diagnosis is ALL. And you all are right. CLL never occurs in this age group. Occurs after 80 years. Reading the age only, rule out this option. Reading the age, don't look at the image. Reading the age only, rule out this option. Rule out, rule out. It never occurs in children. In children, we have only one leukemia, ALL. And the image is also supporting that. Say yes if you all got it. The correct answer is A. So, based on that, you get many age-based questions. So, till now, we have covered three. Till now, we have covered three leukemias. So, age group is different in all three. Okay.

So, let me come on the last one. Are you ready? Shall I start the last one? CLL. And I will do a comparative analysis of all four. So, let's come on the last one that is CLL. So, let's come on the last chronic lymphocytic leukemia, also known as small lymphocytic lymphoma. Sometimes this converts into lymphoma. So, it is CLL or SLL, one and the same. Age is over 60 years. Median age is 60 years. It occurs in old age only. So, usually 60 years or more than 60 years. Okay. So, here what is happening? Listen, listen, people. Come back. Listen, everyone, listen. Start from the beginning. So, start from CML. What was happening in CML? In CML, the five cells were mutated. These five, they all were mutated. They were doing uncontrolled mitosis, and they all five were coming in the blood. That is the CML. We have seen that. Okay. Now, the second I taught you is AML. In AML, only myeloblast was mutated, doing uncontrolled mitosis, and it was coming in the blood. So, in AML, only myeloblast was coming in the blood. Okay. The third I taught you is ALL, in which lymphoblast was doing uncontrolled mitosis. It was mutated, and only lymphoblast was coming in the blood. That is ALL. Now, last I want to teach you CLL. So, you tell me, in CLL, what will come in the blood? You tell me, in CLL, what CLL will come in the blood? Can you guess? Then I will tell you. So, what will exactly come in the blood? Can you tell me what will come in the blood? Huh? Say yes, say no. Say something. Respond, people. Write down in the chat box, fast, quick. What will come in the blood? Here, none of the blast will come in the blood. In CLL, mature lymphocytes come in the blood. Mature lymphocytes come in the blood. CLL, you will see, ma'am, we all have lymphocytes. I'm also having lymphocytes, but I don't have CLL. So, what do you mean by mature lymphocytes? Here, the mature lymphocytes are there, but they are not normal. They are mutated lymphocytes. In that, mutations are there. I will tell you the exact mutations are there. No, no, no. Lymphoblast don't come here. Bisma, it is the only leukemia where no blast is coming. Neither myeloid nor lymphoblast, none of the blast is coming. Here, the mature lymphocytes, which are mutated, they are coming in the blood. And in the blood, you will get only one type of cell, that is mature lymphocytes. Not lymphoblast, mind you. Only mature lymphocytes. Again, school uniform appearance, but only one cell, lymphocytes, not a lymphoblast. If you're getting only lymphoblast, it's ALL. You are getting mature lymphocytes, it's CLL. You are getting my point? So, here, basically, the mature lymphocytes, this mature lymphocyte, it is not normal. It is not normal. Normally, we have 20 to 50% of lymphocytes in blood. Here, 99% are lymphocytes. Most of the cells are only lymphocytes. No neutrophil, no eosinophil, no basophil, nothing else. So, here, the complete marrow is filled with lymphocytes, which are abnormal, mutated, and it is spilled in the blood. Tell me the mutation. There are five mutations. Deletion of 13, deletion of 11, deletion of 17, 11, 13, and 17. The odd numbers and the trisomy of 12. So, deletion of 11, 13, and 17, I mean, monosomy, monosomy of 11, 13, and 17, but the trisomy of 12. Okay. So, these are the deletion of 13 is most common, that will lead to, you know, that will lead to uncontrolled mitosis and lymphocytes, and the lymphocytes are spilled in the blood. So, here 99% cells are the lymphocytes. You got it? So, here also the same three clinical features: anemia, bleeding disorders, infection, because here most of the cells are lymphocytes, they will replace everything else. So, no RBC, patient have anemia. No platelet, patient have bleeding disorder. And most of the cells are only mature but abnormal lymphocytes. So, patient have high susceptibility for infection. But lymphadenopathy, hepatomegaly, splenomegaly can also present. Okay.

Lab diagnosis, of course, hemoglobin and platelet will be less. And WBC will be normal to more. You can see here, this is the peripheral smear. Now, compare this, ma'am. Okay. What is this? Listen, this. Understand this. This is a patient. The age of the patient is 80 years. Okay. The age of this patient is 80 years, and patient is complaining of anemia. Patient is having lethargy. Patient is having bleeding disorders. Patient is having frequent infection and lymphadenopathy. So, looking at the age and the symptom, I'm suspecting the patient is having leukemia. So, what I will do? So, take a peripheral smear, and I'm suspecting the patient is having CLL. And my diagnosis is right. My suspicion is right. If my suspicion is right, the blood sample contain only one cell. Which cell? Is it lymphoblast? No. No. It is lymphocyte. Only one cell. The mature lymphocytes which are mutated. So, this, this, these all cells are mature lymphocytes which are mutated. Now, please listen. They are mutated. They are abnormal. They are not normal lymphocytes. Their cell wall is very fragile. So, what happens after taking it in a test tube? What you will do? Say, ma'am, I will make a smear. I will take a slide. How to make a smear? Tell me the process. Say, ma'am, it's very easy. Take a drop here. Take a drop here. And take a spreader. At 45 degrees, put the spreader and spread and make a tongue-shaped smear. I guess you know that. So, you take a spreader and with a spreader, you make a smear. So, why I'm telling you that? So, because here, when you spread and make a tongue-shaped smear, now most of the lymphocytes, sometime they get ruptured because they are abnormal lymphocytes. You get my point? So, here you get the complete lymphocytes in the test tube. But whenever you transmit them on a slide and spread them, some of them are complete, but some of them will rupture. Some of them will rupture. They will burst. The bursted lymphocytes are known as smudges. It's known as smudge cell or also known as basket cell. How many of you got it? Smudge or basket cell are the ruptured lymphocytes. You will get them in the slide, but you will not get them in the test tube. So, you can see it's a slide artifact. It's a slide artifact. These are not present in patient. Smudge cells are not present in patient's blood. They are not present in test tube. But while making the slide, because of the spreader, the lymphocytes get ruptured because they are abnormal lymphocytes. And they will get ruptured and they will make the smudge, smudge cells or basket cells. How many of you got it? So, in this slide, what you will get? You will see, ma'am, these all are mature lymphocytes. Only one type of cell, uniform mature lymphocytes. But some of them are ruptured, and I can see this is a smudge cell. This is a smudge cell. How many of you got it? You can see the same here. You can see only one type of cell, mature lymphocytes. Small lymphocytes, you can see. And some of them are ruptured, which are known as smudge cells. Smudge cells or basket cells. How many of you got it? People, say, people, respond. So, smudges or basket cells are the degenerated forms. They are produced because of the fragile lymphocytes. The lymphocytes are very fragile. They get ruptured. You get MCQs on that. Yes. Due to vimentin problem. Absolutely right. Uh, Clary. Absolutely right. So, in the cell wall, uh, in the cell wall, I told you, there is a problem in the vimentin, and that's why they are very fragile, and by making a slide, they get fractured. So, that is the smudge cell. How many of you got it? So, we are done here with the peripheral smear also. So, we can compare all four. Finally, finally, we can compare all four. The four leukemia peripheral smears in front of you. Let's compare. Come back. Let's compare. You can see these two are myeloid. These two are lymphoid. You can see the acute, chronic, acute, chronic. In AML, let's start with AML. In AML, compared to ALL, compared the two acute versions. In the two acute versions, both of them are school uniform appearance. Here, only one cell, myeloblast. Here, only one cell, lymphoblast. You will say, ma'am, how to differentiate myeloblast from lymphoblast? Myeloblast have moderate cytoplasm with Auer rods, that is Auer rod cells. Here, scanty cytoplasm or no cytoplasm and no Auer rods. So, myeloblast, lymphoblast, that's it. Now, coming on the chronic versions. Coming on the chronic versions. See the chronic version of CML here. See the chronic version of CLL here. See the chronic versions. So, in CLL, it's a garden party appearance. You get many types of cells, especially the five precursors: myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form, along with neutrophil, eosinophil, basophil, and monocyte. You get everything, garden party. And here, again, full uniform, but no blast. Here, we have blast. Here, we have blast. Here, we have blast. Here, we have no blast. And in CLL, we have mature lymphocytes. It's not a blast, but it's abnormal. It's mutated. And the ruptured form is the smudge cell. So, we can get smudge cells. So, you see the peripheral smear and compare all four. Give me a thumbs up, people. No one will simplify the super simplified version of leukemia. Here, the comparative, you can, looking at the peripheral smear, you can make it out which type. Now, tell me the age of all four. Tell me the pathogenesis of all four. Likewise, everyone got it. Huh? Everyone? Yes. Definitely, will schedule a session on the lymphoma if many students are demanding the same. Okay. Okay.

Now, coming on the lab diagnosis of CLL. Let me finish CLL. Let me. So, in the blood picture, hemoglobin is less, platelet is less, WBC is more, and the cells are most of the cells, I told you, they are lymphocytes. Immunophenotyping, you can do. So, it is a leukemia of the B lymphocytes. So, here all the markers of the B lymphocytes are present, like CD19, CD20, surface IgM, IgD, along with CD23 and CD5. These are B cell markers because here the mature B cells are present now, which are mutated. And lymph node biopsy, you can do. In the lymph node biopsy, you can see the pseudo-follicles can be present. Normal follicles are absent. And instead of that, pseudo-follicles are there. And you can see if you, if you zoom out, if you are zooming it and doing the magnification, inside the pseudo-follicles, you can see the small, round lymphoid cells with scanty cytoplasm. That's it. Okay. We are done. Treatment. No treatment available. Palliative, symptomatic treatment. No chemotherapy, no treatment, no targeted therapy, nothing is available. Prognosis is usually very poor. The poor prognostic factors are 11q deletion, 17q deletion or trisomy 12. No somatic hypermutation or presence of NOTCH mutation. These are the poor prognostic factors. We are done. Read the question. Tell me the answer. 80-year-old man. Look at the age. Age is always important, people. Age is always important. Presented with a painless cervical lymphadenopathy, and the peripheral smear is given to you. Look at the age. Look at the symptom. Look at the image. Combine the three and tell me the diagnosis. What you see in the image? In the image, I can see only one type of cell. These are lymphocytes. You can see these are not blast. Blast are big in size. They are small, small. They are not blast. They hardly have any cytoplasm. And along with that, the biggest clue given to you, the ruptured versions are given to you, that these are the smudge cells. So, lymphocytes with small cells, with this age, with this symptoms, it is CLL. The correct answer is C. And you all are right. Okay. Got it. Can we go ahead? Can we go ahead? Smudge cells are found in. Of course. The question is very easy. I guess everyone can answer. Smudge cells are found in CLL. Of course. So, smudge cells are the ruptured, ruptured mature lymphocytes. That is the smudge cells, also known as basket cells. The basic mutation is in the vimentin. There is abnormality in the vimentin. That's why it gets ruptured while we are making the smear. So, it's a slide artifact. In CLL, basically, which type of cell is predominating? Is it B lymphocytes or T lymphocytes or is it simple lymphocytes or is it monocytes? So, basically, it's a simple lymphocytes which is proliferating here and coming. It is mutated, proliferating, and spilled over in the blood. So, we are done. We are done with the four types of leukemia. Can we compare it once for a while and end the session? You can text me further more sessions you require on which topic, and let me tell you what I have planned further for you. So, let me compare the four leukemias first. You know the definition. Tell me the age group of all four. So, CML occurs after 50 years. AML occurs 15 to 40 years. ALL occurs in children. And CLL occurs 60, 60 to 80 years. So, you can see the age group is entirely different. Okay. Please note down. Looking at the age, exceptions are there, but looking at the age itself, you can have a guess which type of leukemia they are talking. In the pathogenesis, tell me the mutation here. Here, the mutation is taking place in five cells. Tell me first cells: myeloblast, promyelocyte, myelocyte, metamyelocyte, and band form. I will tell you the mutation also. Here, mutation taking place only in myeloblast. Here, mutation taking place in lymphoblast. Here, mutation taking place in mature lymphocytes, not in blast. Now, tell me the mutation. Tell me the mutation, people. Here, only one mutation is there. 9-22 translocation, only one mutation is there. Here, various types are there. Specifically, eight types are there. So, mutation is important in M2, M3, and M4. Although mutation occurs in all, but important in our syllabus is these three. So, in M2, it's 8-21 translocation. In M3, it's 15-17 translocation. And in M4, it's inversion 16 translocation. Okay. Here, in ALL, in lymphoblast, we have two types. We have two types. What are the two types? We have B, pre-B cell and T cell. In the pre-B cell, it's hyperploidy, hypoploidy, and 9-22 translocation. In the T cell, it's NOTCH mutation. You will see, ma'am, we have 9-22. Yes, we have 9-22 here also, here also. So, we have fusion formed there also, there also. But here, the size of the fusion gene is 210 kilodaltons. And here, the size of the fusion gene is 190 kilodaltons, based on which we can differentiate. Coming finally on the mutations in CLL. So, we have 11, 13, and 17 monosomy, their deletions or monosomy, deletions or monosomy, and 12 trisomy. The most important among them is 13. So, this is the pathogenesis you have to learn. Say yes, people. Say yes. So, I have taught you the age of all, and I have taught you the pathogenesis. So, here you have to understand one thing. This mutation, whatever I have mentioned, this mutation, this mutation, this mutation, this is occurring in myeloid cells. So, here all these five cells come in the blood. So, garden party appearance. Here, only one cell comes. Here, only one cell comes. And here, also one cell will come. So, these are the school uniform appearance. But here, along with the lymphocytes, they will rupture. So, you will get smudge cells also. So, comparing the peripheral smear of all four makes sense. You can see that we can compare the peripheral smear. So, you can see here, we are getting only one cell, that is myeloblast, here with Auer rod. Here, getting one cell, lymphoblast, no Auer rod. Getting five cells: myeloblast, myelocyte, promyelocyte, metamyelocyte, and band. And here, getting only one cell, lymphocyte, but their ruptured version, smudge cell. I guess it's crystal, crystal, super duper clear to all of you. So, peripheral smear is super duper clear to all of you. Now, the most important thing, one more thing, wait. Clinical features. Compare the clinical features of all four. We will compare every aspect, every aspect. I will make leukemia as a, you know, I will crush it, and definitely I will make it a fun for you. After 5 minutes, leukemia will be nothing for you. You know, you can answer any question based on the leukemia in whatever exam you are targeting, doesn't matter. Oh, anyways. So, here, clinical features. So, anemia, thrombocytopenia, that is bleeding disorders, and infection, that occurs here also, here also, here also, here also, because here the five cells are replacing everything. Here, myeloblasts are replacing everything. Here, lymphoblasts are replacing everything. And here, lymphocytes are replacing everything. That's why patient have anemia in all three. Patient have thrombocytopenia in all four. Patient have infection in all four. So, this is common in all four. But here, we don't have organ infiltration. But here, we have organ infiltration. So, lymphadenopathy occurs in both of them. Hepatosplenomegaly, bone pain occurs in both of them. Okay. It is a pre-organic. Here, specific organs in AML is gum and chloroma. Here, specific organs is mediastinal lymph nodes, testes, and meninges. That is specific. Meninges occurs here also, but less specific. So, that you have to learn. Sometime here, cervical lymphadenopathy or other lymphadenopathy present here also, but only lymphadenopathy. So, this is the organ infiltration we have seen. But we never have organ infiltration in CML. Please learn that. In CML, no organ infiltration. Coming on the lab diagnosis and treatment part. Okay. Coming on the lab diagnosis of all of them. Let me tell you the lab diagnosis. Let me erase it and tell you the lab diagnosis. Okay. In the lab diagnosis, you tell me the cytochemistry, I mean, special stain of all of them, on which you frequently get the question. So, here the special stain is NAP or LAP score, which is reduced here to differentiate from leukemoid reaction. Here, it's M0 positive, Sudan Black positive, and NSE positive. Okay. These three things are negative here. But this one is

pass positive and acid phosphatase positive, which are negative here. And know, and here we don't have any special. We have imminochemistry here. We don't have cytochemistry. So it's CD19, CD20, IGM positive, I know surface marker CD23 positive. So you have to learn the imminochemistry. Treatment portion, I have told you. So only one of them have targeted therapy, CML, and the name of the targeted therapy is imatinib. Here we have imatinib. We don't require bone marrow transplant here. Bone marrow transplant with chemotherapy. Bone marrow transplant with chemotherapy. Here palliative therapy. Prognostic factors. You have to learn good, bad, good, bad, good, bad, good, bad. Got it? Huh? Give your feedback. You got till you give me ask. Was it easy? The same you can compare here also. If you didn't like this diagram, you can see the same here. Appreciate. Appreciate. Appreciate my blast here. Appreciate the Auer rods. Appreciate lymphoblast here. No rods. Appreciate all myeloblast, pro, and appreciate only one cell that is lymphocyte along with the smudger cell here. Appreciate if you have any doubt, ask. If you have any doubt, please ask. Got it? Got it.

Now, if you are preparing for your competitive exam, that is NEET PG in India, FMG, INIC in India, or you are preparing for some abroad exams like USMLE or PLAB. So, I have simultaneously we have solved the MCQs. But if you are preparing for second pro university exam and you have a theory paper on leukemia. So this is a list of university exam questions. I will provide you in the notes. You can read the long questions are provided to you from leukemias. You should be prepared for that, and short questions are also provided to you. So, all the long questions, short questions, and damn sure you can answer it now. So, whatever exam you are targeting, you are prepared people. You can note down this contact number. If you have any query on this topic, or if you have any query on any other topic which I taught you in pathology, in pharmacology, in microbiology, in PSM, in medicine, whatever subjects I taught you in that, you can text it here. It is not for calling. It is only for chat support. So, please kindly don't call, and you, you, you have a chat support here. The number is 983032948. You can note it down. You can save it with my name, and I personally answer each of them. But sometimes the response can be delayed by a day or two. But definitely, you will get the response. Okay?

If you have any topic in your mind and you want me to teach that on YouTube. So, instead of writing here in the YouTube comments, please text it here. So, please text that topic. If this the same topic is demanded by many students, we will schedule it soon. But if it is demanded by less students, we will also schedule it, but later on. Okay? So, that will be the sequence we will decide. Okay? So, team will decide the sequence. Okay? So, please text whatever topic you want, it's in your mind, in whatever subject, please. Okay. So, please text it here. Okay. Got it. Okay.

If you want the notes of this session, or notes of any other session which I have taught on the YouTube. The notes are free. They are not chargeable. They are available. So, you have to click on the link which is pinned in the comment box. After the session, it will be pinned. I mean, just after the session, you can check. Maybe my team have pinned it. If it is not pinned, definitely after just immediately after ending the session, you will get it. Okay. The same replica which I have taught you right now. The same replica you will get. Okay. Exactly same. Okay. So, you can get the notes.

Now, you can do a scan here. So, the QR code is provided to you. You will be diverted to my website, that is med by Dr. Priyanka, where I share the updates and high yielding educational content which is important for the medical specifically. Okay. No fun, no funny videos, nothing, only high yielding educational content which is important for you. So, you can connect with me on various social media platforms, on WhatsApp, on Instagram, on Telegram, if you wish. So, just scan it, or you can take a snapshot, you can scan it later. That's all about it. Thank you for your time, for your attention, for your patience. Thank you so much.

What about the next sessions we have scheduled? So, currently in the February, we are having these eight sessions. This one is already done, and today we have covered this complete leukemia in one shot. Today, 7th of February, I guess, after 12, it's already 8th. Anyways, um, on 12th of February, again, the same timing, 10:00 PM, 10:00 PM, complete contraceptive devices in one shot. Now, you have contraception in multiple subjects. Sometime you read it in OBG, obstetrics and gynecology, you read it in community medicine. You read in multiple subjects. I will compile all of them at one place in one shot, and you get many questions from the contraceptive devices. So, we will compile and compare, and we will do a more simplified version of that. After that, we have a session on hypersensitivity. We have a session on triage. We have a session on thalassemia. This month only, we have, I'm going to compile complete mycology in one shot on huge demand of students, all fungus at one place in one shot, and we have a session on all pharmacokinetics, important things in entire pharmacology, pharmacokinetics at one place in one shot. So, these all are important sessions this month. You can take the snapshot. The timing of all sessions is same. It's 10:00 PM onwards in the night, 10 to 12, 10 to 1, whatever, 1:00 AM approx. So, 2 to 3 hour session because in the late night, students are more, you know, awaken. I have seen, huh? The late, most of the students nowadays, they are late night hours, I have seen instead of early morning, I know wake up. So, that's why we have scheduled the sessions late night. Thank you so much. Good night. I hope you have enjoyed the session. You have learned a lot of it. So, don't forget to share your feedback. It's important for us to improve. Thank you so much.

And to be, if you want to be odd one, you, if you want to be number one, you have to be odd one. So, never, uh, be afraid if you are different from others. Never be afraid. Okay. So, thank you so much. Bye-bye. Good night. All the best. So, I am ending this session and, uh, just a second, give me a minute. I would like to wish best of luck to the students who are going to appear in the exam in the next few months. Many students, second MBBS students texted me to take this topic because they are going to appear in the exam this month, next month, in the next few days. So, on huge demand, I have scheduled this. So, I want to wish best luck to all those students. Thank you so much. Wishing all the best to all of you. Bye-bye. Good night.