let’s say that you’ve got this hematopoic stem cell and this guy’s basically starting his Choose your own adventure game. It can choose to differentiate into a myeloid stem cell or a lymphoid stem cell. Sometimes we just call these precursor cells blasts. If it goes the myeloid path, it can go on to be all sorts of specialized cells like red blood cells, monocytes, granuloccytes or megaaryiocytees. Alternatively, it could choose the lymphoid stem cell route and it can go on to become B cells or T- cells of the immune system. These adventures of the hematopoic stem cells are usually happening all the time and new cells are like always being created in acute leukemia, though they lose this ability to differentiate or mature into one of these cells. So for example, they might get to the myeloid blast part of the adventure, but can’t differentiate any further.
And when they can’t go anywhere they start to build up. So you end up with this buildup of these blasts or stem cells, and since this is all happening in your bone marrow, this buildup will also happen in your bone marrow. So if you took a sample of somebody’s bone marrow that didn’t have acute leukemia, you’d probably notice that the percentage of their blast cells is about one to two percent, which would be normal.
If there are greater than 20 percent blast cells in the bone marrow though we define that as acute leukemia. When all these blast cells start to build up, they get crowded and they crowd out or sort of get in the way of normal cells differentiating. So what happens is you end up presenting with a loss of cells that you’d normally produce in the bone marrow, like if you had a loss of red blood cells you develop anemia or you might have symptoms of fatigue or maybe you’re missing platelets. So you get thrombbocyoppenia and have problems with bleeding or neutrophils and neutropenia and start getting more infections. Usually symptoms like this can come about relatively quickly, which is why we say that it’s acute leukemia.
Eventually these blasts build up to a point where they start to spill out into the bloodstream which typically causes your white blood cell count to go up. So if you took a peek at a blood smear there’s a couple things to look for. First look at how large these guys are compared to the normal cells. Another thing is that they’ll be pretty immature judging by this relatively low amount of cytoplasm.
So we figured out that it’s a blast cell, but what kind of blast cell is it lyhoid or myeloid? H. Tough to say this is important though, because if they have a buildup of myloblasts, they’ll actually have acute myeloid leukemia, whereas if they have a buildup of lymphoblast, they’ll have a cute lymphoblastic leukemia and these two are very different and need very different treatments. So what we’re going to do is we’re going to look for certain markers for the lymph blast, the most important markers that they’ll have this positive nuclear standing for TDT in the cell’s nucleus. TDT is a DNA polymerase that’s present only in the nucleus of the lympholasts, not in the lymphocys or the mature cells, and not in the myloblasts. So if a nuclear stain comes out positive for tdt, we know that it’s got to be a lymphoblast right.
For the myloblasts presence of Mylohyoideus peroxidase and enzyme. Indicates that we’ve got to have a myeloid blast on our hands. Usually this is done by cytoplasmic standing but you can also look for this like crystallized version of the enzyme called an hour rod under the microscope.
So let’s say that we’ve got a positive test for DNA polymerase TDT meaning that we’ve got a lymphoblast. So we must have a cute lymphoblastic leukemia. It actually gets a little more complicated though, remember the lineage where lymphocytotoxicity blasts go on to be either B or t-cells. Well in between, they become either B lymphoblasts or T lymphoblasts. So really you can have subtype B acute lymphoblastic leukemia or ball or T acute lymphoblastic leukemia or tall. Just like we figured out that as a lymphoblast with TDT positivity, we can also determine which subtype of lymphoblast. It is based on surface markers.
The most commonly seen are these B lymphoblasts. SO. BAAL and Super. Important and specific service markers to look for are C-TEN, c-nineteen and c-twenty. Treatment of BAL usually involves chemotherapy and there’s usually a very good response, but one thing you have to remember is that the chemotherapy goes into the blood and it can’t cross either the blood brain barrier or the blood testicular barrier. So patients will often need prophylactic injection of the chemotherapy to the scrotum and the cerebrospinal fluid.
If we look at these patients a little more closely at their cytogenetic abnormalities, so like abnormalities in their chromosomes, we can get an idea of their prognosis. If they have a translocation of chrosome 12 and 21 or t- 1200 and 21, they’ll usually have a pretty good prognosis, and this tends to happen more in children. A 922 translocation or sometimes called ph positive or the Philadelphia chromosome, on the other hand, is a pretty poor prognosis, and this one’s seen more in adults.
For the t-lymphoblastic sword. They’ll usually express surface markers that range from cd-two to cd-eight. Unlike BAAL, these blasts do not express cd-ent. So luckily we’ve got some helpful pneumonics with tall. It usually presents as this thymic mass in the mediaineum, so T forth thymus and this happens most often in teenagers. T for teens. So we’re going to call this acute lymphoblastic lymphoma. Wait. Why not leukemia? Well remember that for leukemia, the malignant cells float around in the blood, where lymphoma means that the malignant cells are forming this mass. So in this case it’s called lymphoma since it’s forming this thymic mass.
So that’s ALL for the ALL type. Let’s switch gears to the AML type, which is this accumulation of miloblasts. Remember that we’re looking for an enzyme called Mylohyoideus peroxidase which can present as these hour rods. Like in this picture, this structure right here is an hour rod which is basically like this crystallized aggregate of myloprooxidas which is only found in myloblasts. AML, unlike ALL is more common adults between the ages of 50 and 60 and can actually be subclassified in three ways, either again by cytogenetic abnormalities the lineage of the myloblasts or by surface markers. One important subtype of AML to be aware of is acute promylocidic leukemia and this is characterized by translocation of chromosomes 15 and 17. So right now we’re subclassifying based on cytogenetic abnormalities chromosomes 1517. This translocation ends up disrupting the retinoic acid receptor which hurts the cell’s ability to mature. And you get this buildup of promylocys.
These cells also tend to have a lot of hour rods which increases the chance of coagulation which makes it a medical emergency due to the risk of disseminated intravascular coagulation or DIC. One way to treat promylocidic gluukemia is with Allan retinoic acid or ATRA which is this derivative of vitamin A and this guy binds to the disrupted retinoic acid receptor and actually causes these blasts to mature into neutrophil which eventually go on to die but it does sort of lift some of the leukemic burden since there aren’t many of these blasts floating around.
So that one was characterized by its cytogenetic abnormalities right. But we can also characterize by the lineages. So sort of just like lymphoid blasts can go on to be either T or B lymphoblasts. You could have an AML like erythroblast AML or megaaryoblasts or monoblast AML ALL which would involve this proliferation of that type of cell. So one that’s important to know about is this last one monoblast AML or acute monocidic leukemia. So these monoblasts build up and they actually often lack myloprooxidas. But what we can look for instead is this infiltration of the patient’s gums? So check out this image. Notice how this patient’s gums are clearly swollen, and this is a classic sign of acute monocitic leukemia.
Another important subtype though is megaaryolastic leukemia, so a buildup of megaaryoblasts just like the monoblasts. These don’t have myloprooxidas either, but there’s this association with Down syndrome before the age of five, so this is actually an important point. In general, patients with Down syndrome have an increased risk of acute leukemia usually acute megaaryoblastic leukemia when it’s before the age of five and all after the age of five.
Now there are also conditions that aren’t necessarily AML but can actually lead to AML and one is called myloysplastic syndrome which is characterized by this abnormal buildup of blasts in the bone marrow which sounds familiar right but at this point it’s below 20 percent so we don’t call it AML yet. Milo dysplasia meaning bad formation of bone marrow cells often leads patients to have a low blood cell cone since the cells aren’t developing right which is also called cyoppenia. Because they have these cyopenass, they often actually die due to infection or bleeding, but they can also progress to acute leukemia if their blast percentage goes over 20 percent so then they’d have something like AML with a background of miloysplasia and that’s an overview of acute leukemia as well as some of the more common subtypes of acute leukemia.