Precursor cell

Transcription

Voiceover: So your next patient just walked in, and his name is Joe. And he's here because he hasn't been feeling so well. He tells you that for the past few weeks, he's been feeling really tired. So just not like his normal self. And he thinks that he's lost some weight. So you check up on that, and you find out that he's actually lost a significant amount of weight. And he looks a lot thinner and weaker than he usually does. So you talk to him, you calm him down, and then you start to examine him, and right away you notice that his skin looks a lot paler than it usually does. So this is what Joe normally looks like, but today he looks a little bit more like this. And you notice that he has bruises all throughout his body. And when you ask him about the bruises, he actually can't remember getting them. He doesn't remember ever getting hurt. And when you check his temperature, you see that he has a fever. So as you're finishing your exam, he tells you, "Well, you know, I've been feeling this pain "throughout my body, and it feels like the pain "is inside my bones, and inside my joints." So he's also been having some bone pain. So if you're worried about Joe, then your instincts are on pointe, because there's definitely something serious going on over here. But at his point, you probably don't know what that is. Is this infection, is it cancer, is it some rare, crazy disease? It's really hard to tell at this stage. So you might start off by ordering some basic studies, some basic labs, and one of the labs that you might order would be a CBC. And a CBC stands for Complete Blood Count. And it's a really cheap and easy test to get, but it tells you a lot of information. So this is the typical information that you get from a CBC. So it tells you the number of red blood cells that you have, it gives you your hemoglobin, and your hematocrit values, which are indirect ways of measuring how many red blood cells you have, it'll give you a platelet count, and it'll give you a white blood cell count. And these are the normal values, just for reference. So hint, hint, Joe has leukemia, but we don't know that yet, because we're still working him up. So a CBC shows us that he has a decrease in his red blood cell count, and that's called anemia. And he also has a decrease in his hemoglobin and hematocrit. And that's just from the decrease in the red blood cell numbers. And he also has a decrease in his platelet count, and that's called thrombocytopenia. And finally, he has a decrease in his white blood cell count, and that's called leukopenia. But actually, in leukemia, you could also see an increase in the white blood cell count. And that's because in leukemia, eventually the leukemia cells run out of space to grow inside the bone marrow, and when that happens, they leak into the blood, and you start to see them in the blood. And these leukemia cells are usually immature white blood cells, just because most leukemias are white blood cell leukemias. So the person who's counting all of these cells, who's giving us our CBC values, sees these immature white blood cells, sees these leukemia cells, and he or she counts them as white blood cells. And that's why you have an increase in the white blood cell count. But if you looked more closely at the blood, you'd actually see that the number of healthy mature white blood cells is always decreased. So this CBC is really concerning. It tells us that our patient, Joe, has a shortage in the number of all of his blood cells. And that actually accounts for most of the symptoms that he came in with. So you should feel like you're heading in the right direction towards finding out what's wrong with him. And you might wonder, well what's causing the shortage in blood cells? Is the bone marrow not making enough blood cells, or is the bone marrow making enough blood cells, but then the cells are being destroyed after they're released into the blood? And really, the only way to answer that question is a bone marrow aspiration. So if this is a bone over here, you could stick a needle inside the bone, and inside this cavity in the center of the bone, which is where the bone marrow is. And with this needle, you could then draw out some fluid, and then you could look at that underneath the microscope. So in leukemia, what would you expect this fluid, the bone marrow aspirate, to look like? Well, I'm gonna give you a couple of seconds to think about that while I draw the answer. So, I've drawn this diagram like 1000 times already, but I just wanted to remind you that in leukemia, your immature blood cells, your crazy leukemia cells, take over the entire bone marrow. So much so, that there's no space left inside the bone marrow. So if you took a sample of this bone marrow, it would show you two things. So the first thing that it would show you is lots and lots of cells. So an increase in the number of cells, compared to what you normally expect to see. And so we call that a hypercellular bone marrow. And hyper just means a lot, and cellular means cells, so hypercellular bone marrow means a bone marrow with lots of cells in it. And that's exactly what you get with leukemia. And the second thing that you'd expect to see is lots of immature blood cells, which are called blast cells. In a normal bone marrow, do you see immature blood cells? Well sure, because the mature blood cells have to come from somewhere. They come from the immature blood cells. But in normal bone marrow, only two to three percent of all of the cells are immature, only two to three percent. But in leukemia, the number of immature cells is greater than two to three percent. But it's not enough to say that it's just greater than two to three percent, we need to quantify how much greater it is. So in leukemia, more than 20 percent of all of the cells in the bone marrow are immature blood cells, or blast cells. So if we do a bone marrow aspiration, and we see that more than 20 percent of all of the cells that we're looking at are immature cells, are blast cells, then we know definitively that the patient has leukemia. So you figured out what's wrong with your patient, you diagnosed him with leukemia, but it's not enough to stop there, because you have to figure out what type of leukemia he has. And that's important for being able to tell him what his prognosis is, and for being able to determine what his treatment should be. So the next step would be to classify the leukemia. And this can be done in one of two ways. The first way seems the most intuitive to me. And that is to look at the leukemia cell, to characterize the leukemia cell. So I want to take you back to this diagram, which we used to talk about the development of the different types of blood cells, and you can see the mature blood cells down here. And you could tell these cells apart in a snap. They have such distinctive appearances. But these blood cells up here, the immature blood cells, these cells pretty much look exactly the same. So you can't tell them apart just by looking at them. And remember that leukemia cells are immature blood cells. So they look like these guys. So going back to our leukemia cell that we're trying to characterize, looking at the cell isn't gonna be enough. We're gonna need to do more to try to figure out what type of cell it is. So in order to find out what type of cell this is, we look at what molecules this cell has, both on the outside, and on the inside, because different blood cells express different molecules, different unique molecules that allow us to identify them. So I want to give you an example. So for example, lymphoblasts, which are immature lymphocytes, so immature B and T cells, have this protein inside their nucleii, and that protein is called TdT, and only the lymphoblasts have this protein, so the mature lymphocytes don't have this protein, and all the other types of blood cells don't have this protein. So if Joe's leukemia cell comes back positive for TdT, we know that his leukemia came from, it originated from, a lymphoblast. Another famous example is a myeloblast. Now remember that these are the immature blood cells that make the neutrophils, eosinophils, and basophils. This is a myeloblast, and a myeloblast has this protein, this enzyme, in its cytoplasm that's called myeloperoxidase. And myeloperoxidase you'll often see abbreviated as MPO. And we can actually, we have a paint, we have a stain, or a paint that binds to myeloperoxidase. So we can take the leukemia cells from our bone marrow aspiration, and we can flood them in this stain, in this paint. And if the cells take up the stain, if they become colored with the stain, we know that the patient's leukemia originated from, it developed from, a myeloblast. So that's the first way that you can classify your leukemia. The second way is by looking for chromosome translocation. Now remember a chromosome translocation looks something like this. And we said that a lot of leukemias are associated with chromosome translocation. So you can look to see if your leukemia cell has a particular chromosome translocation that's associated with a particular type of leukemia, and that can help you classify the type of leukemia. And so this is how you diagnose leukemia.