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Video transcript

Myelodysplastic syndrome is usually something that's tucked away into the corners of a textbook, in the section where they talk about leukemias, and it's usually described as being a pre-leukemia. So, a precursor condition to the development of leukemia. and that's not always necessarily the case. That's not entirely true. So, what we're going to do is, we're going to dedicate this entire video to talking about myelodysplastic syndrome, which is usually abbreviated MDS, and we're going to try to clear up whether MDS really is or is not a pre-leukemia, okay? So, let's start off by letting the name of the disease tell us a little bit more about it. So, myelo-, myelo-, myelo- tells us that we're talking about myeloid cells, right? So, we're talking about red blood cells, platelets, neutrophils, basophils, and eosinophils, and dysplastic, I'll use a different color, dysplastic comes from the Greek word, I'll write that here, comes from the Greek word, dysplasia, dysplasia, which means abnormal, abnormal. So, we're talking about abnormal myeloid cells, okay? And that requires some further elaboration. How are they abnormal? Well, let's look here again at the development of a normal blood cell, all right? We've seen this before, a hematopoietic stem cell developing into a mature specialized blood cell. Well, in the case of myelodysplastic syndrome, your immature blast cell, your immature myeloid blast cell, is abnormal-looking, it's very strange-looking, and why does it look so strange? Well, it's because it has a DNA mutation. So, it has a mutation in its instruction manual, in the instruction manual of the cell, and that causes it not only to look abnormal but also to function abnormally, and by that I mean that this cell doesn't mature the way that it should, so it can't move on to the next stage. It's kind of stuck in this immature blast stage, and we've seen this before, right? This is actually the first step in the development of leukemia; however, something that we notably don't see over here is the second step that was required in leukemia, and that was a second gene mutation that would then cause the cell to start dividing rapidly and out of control. We don't see that in MDS, and that means that this isn't a cancer of immature blast cells. Instead, this is a condition in which you have immature blast cells that have an abnormal appearance, that can't mature and develop like normal blood cells should, okay? So, the hematopoietic stem cell, unfortunately, continues to make more of these abnormal blood cells that don't mature, and even if the hematopoietic stem cell is able to make a normal blast cell that is then able to mature all the way down to the mature specialized stage, there's something wrong with these cells, something that we don't quite understand fully yet, in which these mature specialized cells die off quicker, die off quicker than normal blood cells should, and you can imagine that because of these two situations, because of mature cells dying off quicker and immature cells not being able to develop the way that they should, in myelodysplastic syndrome our primary problem is that the bone marrow isn't able to put out as many myeloid cells as it should, so there's a decrease in the number of your myeloid cells, your myeloid cells, okay? And that's really where the symptoms of myelodysplastic syndrome come from, and we talked about that a little bit before, the symptoms that you get when you don't have enough red blood cells or enough platelets or enough white blood cells. So, these patients, unfortunately, require constant transfusions. They require constant supplementations with the types of cells that they're missing, in order for their bodies to continue functioning the way that they should. Now, if the primary problem in myelodysplastic syndrome is that you don't have as many myeloid cells as you should, you can imagine that a patient who has myelodysplastic syndrome presents very similarly to a patient who has leukemia, and that's very true. They present very similarly, and so, if you had a patient presenting with these symptoms, you would go through and order the tests that we talked about. You'd order some blood tests, and then you'd proceed with getting a bone marrow aspiration. So, you'd take a look inside a person's bone. I wonder if I have enough room to draw this, just barely. That's your central cavity that contains the bone marrow, and we said a bone marrow aspiration involves sticking a needle into that cavity. All right, here's my needle, it's a big needle, and drawing out some fluid and looking at the bone marrow underneath the microscope. And now, we said that in normal bone marrow, normal healthy bone marrow, only two to three percent of the cells will be blast. I'm going to put that in a capital B, blast, right, in normal cells, in a normal bone marrow, normal bone marrow. Now, in leukemia we said that we would have greater, because we have a cancer of these immature blast cells, in which they're dividing rapidly and out of control. We have tons and tons of these immature blast cells. So, to put a number on it, we said that we would see greater than 20 percent blast cells. I made that kind of look like a one. Okay, greater than 20 percent blast cells in leukemia, in leukemia. Now, in myelodysplastic syndrome, yes, we would see an increase in the number of immature blast cells, compared to the number of mature cells, simply because these cells aren't maturing, aren't turning into mature cells, aren't turning into these specialized mature cells, right? So, we'd expect to see a greater number of these immature cells, compared to the mature cells. However, because we don't have a cancer of these cells, these cells aren't dividing rapidly and out of control, we wouldn't expect to see greater than 20 percent blasts, as we do in leukemia. Instead, we see less than, less than 20 percent blasts but greater than two to three percent. So, greater than what's normally expected, but less than what's seen in leukemia, and that's what we see in myelodysplastic syndrome. Now, one last point that I'd like to make about this disease is that we said that the cause of myelodysplastic syndrome, this gene mutation that prevents the cell from maturing, was the first step that was required for the development of leukemia, right? So, we had step one already occurring, and you can imagine that if then in this cell you had another mutation develop, that caused the cell to start dividing uncontrollably, that would then lead to a leukemia. It would lead to a myeloid leukemia, right? And since these are very immature cells, it could lead to an acute myeloid leukemia, and that's why people often refer to myelodysplastic syndrome as being a pre-leukemia, because you already have one mutation required for the development of leukemia, all you need is another one, and if you were then to acquire the second mutation, your myelodysplastic syndrome would transform into an acute myeloid leukemia. Now, the only thing is that this doesn't happen nearly as often as we think it does. It's actually quite uncommon. Most people with myelodysplastic syndrome, most patients will die before their abnormal blast cells ever have a chance to acquire that second mutation and transform into acute myeloid leukemia.