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Q. I have a quick question on the cell of origin in leukemia. In our pharmacology class, we went through a section on cancer. There was a slide that said leukemia is a tumor of hematopoietic stem cells. But leukemia involves more than just hematopoietic stem cells, right? I think I remember from our pathology class that leukemia can also involve cells downstream of hematopoietic stem cells.
A. You’re absolutely right! Which means you really understood the heme part of our pathology class! Just to back up a bit: all leukemias arise from hematopoietic cells (either myeloid or lymphoid cells). But not all leukemias arise in hematopoietic stem cells. Let’s take a look.
Some leukemias arise in stem cells.
All of the chronic myeloproliferative disorders, for example, originate in stem cells. As a result, when you look in the blood and bone marrow, you see a proliferation of all different kinds of myeloid cells (red cells, neutrophils, and megakaryocytes) at all stages of maturation (neutrophils, myelocytes, metamyelocytes, etc.).
In most of the chronic myeloproliferative disorders, a particular myeloid cell line dominates (in chronic myeloid leukemia (CML), for example, most of the malignant cells are neutrophils and precursors) – but because of the stem cell origin, there are other malignant myeloid cells present as well.
Here’s a cool thing. You’d think that the stem cell of origin in these chronic myeloproliferative disorders would be a myeloid stem cell, right? I mean, these disorders are composed of all kinds of myeloid cells – so the origin should be a myeloid stem cell.
It turns out that the stem cell involved is actually a very young stem cell – it hasn’t even decided whether it wants to be myeloid or lymphoid! We know this because the characteristic genetic abnormality (for example, the Philadelphia chromosome in CML) is also present in lymphocytes. That explains why when CML evolves into blast crisis, the blasts may be either myeloid or lymphoid.
Other leukemias arise in non-stem cells that belong to a specific cell lineage.
Acute promonocytic leukemia, for example, originates in a promonocyte (a stage of development between monoblast and monocyte). This means that when you look at the blood and bone marrow, you see mostly promonocytes (the cells in the image above with the lovely tissue-paper-like nuclei). Cells of other myeloid cell lineages (like red cells or neutrophils) are not present. These types of leukemias are a lot more straightforward.
Heme mistakes like this are common!
This kind of mis-statement (“all leukemias arise from stem cells”) happens a lot when people talk about hematopoietic diseases. Even the names of diseases are often stated incorrectly (e.g., “acute lymphoid leukemia” or “acute lymphocytic leukemia” instead of “acute lymphoblastic leukemia”). Heme is an area that many people shy away from, for some reason. I love it and find it really straightforward, but depending on how it’s taught, it can seem really confusing.
If you’re struggling with heme, there are tons of heme-related posts here on Pathology Student. You might also find my Complete Hematopathology Guide useful; it covers all the main hemepath stuff in a straightforward, no-BS way.
Learning to read and interpret results from a flow cytometry, if the CD 13 and CD 33 are at 73% would that be postive for AML or do those percents need to be at 100
Flow cytometry interpretation is not always super straightforward. It requires a lot of training – and in our regular pathology residencies, we go through a rotation in the flow lab, but to really interpret the results with skill you need to do a fellowship to get that level of training.
That being said, I have a few thoughts on your question. First, you need to compare what you’re seeing on flow with what you’re seeing under the microscope. Usually, there are a bunch of different types of cells in the sample (not just leukemic cells) – for example, normal neutrophils, lymphocytes, etc. in addition to the population of blasts. So when you look at the flow cytometry, you need to sort out which cells are the blasts, and which belong to those other groups of cells.
Assuming that you are talking just about the blasts, if most of the blasts express CD13 and CD33 (which are usually present on myeloid cells), and lack markers characteristic of other cell lineages (such as lymphoid markers), that would be good evidence that those blasts are indeed myeloid in nature.
Finally, that alone is not enough to diagnose AML. You need to have at least 20% myeloblasts (or blast equivalents, such as promyelocytes) of all nucleated cells in the blood and/or bone marrow in order to make a diagnosis of AML. If you have less than that, you cannot make the diagnosis of AML, and you’re usually in the territory of myelodysplasia (a group of disorders that may have an increase in myeloblasts – but the number is always less than 20%).
I hope that helps! Flow is hard – and it’s probably best to ask this same question to the person who did the flow cytometry study, and ask him/her to explain the results to you. Usually there is a nice little visual diagram to help you understand what’s going on.