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What is chronic myelogenous leukemia?

Learn what is chronic myelogenous leukemia as well as how to identify its signs and symptoms, diagnose it, and treat it. By Raja Narayan. Visit us (http://www.khanacademy.org/science/healthcare-and-medicine) for health and medicine content or (http://www.khanacademy.org/test-prep/mcat) for MCAT related content. These videos do not provide medical advice and are for informational purposes only. The videos are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen in any Khan Academy video. Created by Raja Narayan.

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  • blobby green style avatar for user umal2030
    what is essential thrombocythemia
    (4 votes)
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  • primosaur seed style avatar for user ghada.s.alyami
    At I'm confused because I heard some tutors say mature and some say immature leukocytes? also, what is the difference between chronic myelogenous leukemia and chronic neutrophils leukemia? is CNL a type of CML? or are they different diseases?
    (2 votes)
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    • hopper cool style avatar for user SofiyaMarkova
      it is immature leukocytes (but not only leukocytes because leukemia is a cancer of blood in general though mostly of white blood cells) because: "In leukemia, there is an overproduction of blast cells". blast cells are immature blood cell.

      chronic neutrophils leukemia is leukemia (so too many blood cells) but this time it is specifically too many neutrophils (blood stem cells differentiate into different kinds of cells, and this is one of them)

      chronic myelogenous leukemia is higher up in the differentiation hierarchy, so to speak. It is too many of the undifferentiated blood cells.

      It already differentiated into myeloid cells (in bone marrow and not in lymph nodes as lymph cells), but it is not any specific one as a neutrophil would be

      Note: leukemia is a general term for cancer of blood. The quote states that it is an overproduction of blast cells because that is one of the forms of leukemia. Also, in chronic myelogenous leukemia you may have a proliferation of other granulocytes (which includes neutrophils). But the point is that CNL is specific to neutrophils while CML is more general which could include neutrophils but is mostly characterized by a proliferation of blast cells (which would not be called neutrophils as they have not differentiated into that yet)


      (1 vote)

Video transcript

- Chronic Myelogenous Leukemia or sometimes known as Chronic Myeloid Leukemia is a type of cancer where white blood cells are mass produced in the blood. These cells tend to be of the myeloid stem cell lineage and because this is a chronic leukemia, the cells we see in the blood stream tend to be the more maturer type of blood cells as opposed to an acute leukemia where you have more immature cells in the blood stream. This type of cancer occurs when a very specific mutation happens where a gene that sits on chromosome 22, that's called the BCR gene. The BCR gene is shuffled so that it sits next to a gene on chromosome nine that's called the ABL or the ABL gene. This defect is known as a translocations, so we write translocation of a piece of chromosome nine onto chromosome 22 that for the purposes of drawing here will look something like this where the BCR gene sits on the ABL gene and they're attached together. This new protein is a type of receptor tyrosine kinase that's constantly on, telling cells that they should keep on dividing, which is the whole premise of cancer. You're making more cells than you need. In fact, this translocation that puts a piece of chromosome nine on a chromosome 22 produces a new type of chromosome altogether that's called the Philadelphia chromosome. Named for the university it was discovered at. But the problem here is that now we're going to be producing a whole bunch of white blood cells we don't need. So I'm drawing here the bone marrow, and as you might recall, one of the first things that's produced here is something that's called a pleuripotent. Meaning that something that has the potency or the ability to make plural or many things hematopoietic, meaning related to the blood stem cell. Pleuripotent hematopoietic stem cell. This can produce two different lineages. I'll draw them out this way and we're not focusing so much on this lymphoid stem cell lineage here, so I'll just draw it off to the side. But let's pay better attention here where we have the myeloid stem cell. As you know there are a variety of things that could be produced here, so I'm just gonna draw them out here, but not name all of them. But recall it's these types of cells right here, these white blood cells that we'll see being produced excessively in Chronic Myelogenous Leukemia. Because the defect is really high up, like around here is where the mutation occurs, we'll tend to see an irregular or an unusual amount of platelets or even red blood cells as well. That translates into a couple of key signs and symptoms. Now Chronic Myelogenous Leukemia or CML as it's sometimes referred to has three distinct phases that have different signs and symptoms. First, there's the chronic phase. In the chronic phase, about 90% of patients are asymptomatic, so without any symptoms. Asymptomatic when they're diagnosed, but later in this phase you can have some signs and symptoms such as abdominal fullness, due to the fact that excess platelets or other white blood cells that are being made have to go to your spleen to get processed or even destroyed if there's too many defective ones causing the spleen to become big or for you to have something that's called splenomegaly. Splenomegaly, and the same thing can happen to your liver as you have a higher basal metabolism because of all the extra cells you have in your blood stream. When your liver gets big, we call that hepatomegaly, so in total you could have Hepato-splenomegaly. Other than the abdominal fullness, a common symptom is having a fever and this is mainly due to having an increased number or a white blood cell count because as I mentioned, that means that you're going to have an increased basal metabolism, which is just your metabolism at rest. The chronic phase will progress, and the next step would be what's called the accelerated phase. The accelerated phase and it's called the accelerated phase because you are more rapidly making cells and often times these are defected cells. Those that don't actually work correctly and this is well illustrated when you consider the platelet because these patients can have bleeding and it's because platelets are supposed to clot and make sure you don't bleed when you're cut, but if you're platelets are not working, you will bleed more and these can manifest as petechiae, which are just small dots that you might see, which is bleeding from your vessels or you can see what are called ecchymoses. Ecchymoses, which are just bruising or bruises that occur when you even just bump into things very lightly and so you'll have an accumulation of blood under the skin that'll look like you hit it there much more intensely than you actually had. In the accelerated phase, you could also get a fever, but this time, it's more likely due to opportunistic infections, which just means that microbes like bacteria, or fungi, or viruses see an opportunity to infect a human being or host because the white blood cells are not functioning correctly in the accelerated phase. Finally, the most advanced phase someone can be in is what's referred to as a, or the blast phase, or even the blast crisis. This is characterized by rapid immature cell production which can cause you to have some pretty significant bone pain. Bone pain related to increased production of myeloblasts in the bone marrow. You can also have a fever and this is for the reasons we've mentioned above, either from an opportunistic infection or from having too many of these cells in your blood stream. Now these are just some things you would see on phyiscal exam, but how would we make a more definitive diagnosis? Well, one of the simplest things you can do is get a complete blood count, which may show you that you have elevated white blood cells in the blood stream on the order of something like 50 to 200,000, whereas you should have less than 12,000. You can also take some of the blood and look at it under a microscope and you'd see on this peripheral blood smear that there are a lot of leukocytes, so you've got what's called leukocytosis, which would look like this where you've got a whole bunch of these white blood cells and you can see they're very different from these guys, which are your red blood cells in your blood stream. Let's minimize this guy and go back up to this list right here. One of the other things that you can see that is considered a pretty slam dunk diagnosis is a positive Fluorescent In Situ Hybridization test or a FISH that will light up to show you that there is a Philadelphia chromosome present. Now one thing I should mention at this point, the Philadelphia chromosome, it's present in about 95% of cases of CML, so it's pretty good, but there are some cases that you won't have it. The translocation of taking the BCR gene and putting it close to the ABL gene; now that's present in 100% of CML cases, so you don't have to have the full chromosome translocation just the gene to get CML, but we check for this because it's very commonly present with CML. 95% is a pretty good odds. It would look like this right here. This is a positive FISH, where you've got, for example, green, perhaps lighting up the BCR gene. Red lighting up the ABL gene and you can see very interestingly here there's a green attached to a red so that's the 9/22 translocation we're talking about. Finally, the last thing or the thing we try to avoid to do is what's called a bone marrow aspiration where we inject a big needle into the bone marrow and suck out some of the marrow and look at it under a microscope where you will see an increased number of myeloblasts. Okay, so what do we do now to treat this? Well, if you were with us for our conversation on polycythemia vera or essential thrombocythemia, you might recall some of these cytotoxic drugs like Hydroxyurea or Interferon Alpha and all they do is they make it difficult to mass produce the white blood cell, but perhaps the most important treatment to know for CML is the use of a drug that's called Imatinib, which is one of the greatest successes of science. Long ago, scientists realized that the BCR-ABL translocation produced this unusual receptor tyrosine kinase that kept on telling cells, myeloid cells, to keep on dividing and the idea was if we made a drug that could block this receptor, something that would come in here and sort of bind the receptor and make it impossible for it to communicate with the other types of enzymes or proteins in a cell that signal that signal that it's time to keep on dividing, you could somehow prevent production of myeloblasts and that's exactly what Imatinib does. It prevents this unusual protein from working and as a result, you can actually cure cancer, cure CML from employing this drug and making it so that you don't produce all these extra white blood cells. This was an amazing accomplishment because before Imatinib, the prognosis for CML was pretty poor. Most would be dead in three to five years without this drug, but now when you use it, so with Imatinib, 90% are alive at five years. Finally, coupled to Imatinib because you're gonna block off production of this protein that is actually necessary for division from time to time, you would have to give this patient what's called an allogeneic stem cell transplantation to make sure they have the cells or the protein machinery to continue dividing and producing white cells correctly. CML's a pretty interesting disease and I think what's great about it is that it really illustrates the success of science, kind of looking into what is the protein produced from a defect and what we can do to generate something to essentially cure cancer.