How is acute myeloid leukemia diagnosed?

So there isn't one test. There are a conglomeration of tests that are important to diagnose and understand a specific patient's AML. The first thing that often happens is, in addition to a physical exam of a patient that often isn't feeling well, we'll have some blood work, which will show some abnormalities. If you remember, we talked before about the three main blood types. And so you could have abnormalities in those blood counts that show concern, either too many or too few platelets, anemia, so you're not making enough red blood, or your white count could be very low or very high. And we look under the microscope and see that those white blood cells don't appear mature, normal functioning cells to fight off infection. They often will look immature. And so there's some sign on the blood counts, and then when you initially look under the microscope of a problem, that would lead to working with our pathology friends to more clearly understand the root of the problem. That would take the form of immunohistochemistry stains, where they do special stains on the blood cells and try to understand what are the proteins on the cell surface? Do those cells appear all to be coming from the same clone to be a problem or some other problem? We complement that with a test called flow cytometry that is more specific at looking at exactly what proteins are on the cell surface, and do we have a clone, as we call it, of abnormal cells? In this case, for AML, abnormal, immature cells indicating a problem. We would complement those studies, often with genetic studies, which are of two main types. Traditionally, we grow the cells in the lab, and we try to look at up to 20 cells for standard karyotyping, or cytogenetics is what we typically call it. And that's where we have a cytogenetist look at the actual chromosomes that make up each blood cell and see, do the chromosomes look normal? You and I typically would have 46 chromosomes or 23 pairs, half from mom, half from dad. And so the cytogenetist can grow the cells and look and see, do those chromosomes appear normal or is there underlying damage, which would be consistent with having some type of cancer sometimes, including AML? In addition to that, we have FISH studies. FISH studies are fluorescent in-cytrial hybridization. Is it a little bit more sensitive for genetic testing than just looking at 20 cells? But you have to know what you're looking for. So we tell the lab the type of illness we're concerned with, and they will have a group of specific genetic probes that they can find certain specific common genetic changes that we might see in AML to further our understanding of that particular problem. In addition to those genetic tests, we would now have the molecular testing. Many times that's called an NGS panel, or next generation sequencing. And that is anywhere from 50 to 500 genes that are tested for to see what is being abnormally regulated in that specific patient's blood cells. Do those specific changes relate to anything driving the leukemia in that specific patient? So that can complement the genetics tests to help us understand the specific subtype of leukemia. Is it standard of care for every patient to receive next generation sequencing? It is our standard of care if available at their center to do molecular testing on every patient, yes. There are different platforms for next generation sequencing, but some type of molecular testing would be a standard. Is whole exome sequencing used in AML? Whole exome sequencing, well, can be instructive and help us understand the biology of the blood cancer we're working with. It's not applied at the bedside in patients with AML like it might be in the research setting. It has not evolved to that level yet. Are FISH tests and other genetic tests done with a blood sample or with a bone marrow biopsy? So many times they can be done on peripheral blood samples if it's clear that there are a lot of leukemia cells circulating in the blood. So it is possible. However, typically the standard would be to do a bone marrow aspirate and biopsy to more fully characterize the leukemia at the initiation of therapy. And of course to look for remission would require a bone marrow biopsy to be performed after therapy to prove that the leukemia is on the run. You can't do a remission analysis just from the peripheral blood. What tests are used to diagnose and monitor AML? So the most important test that's done to pick up AML initially is the complete blood count. So generally speaking, patients with acute myeloid leukemia will either have a low white count or a high white count. Interestingly enough, it can be either. Sometimes these immature blasts stay in the bone marrow and the white count actually goes very low. Other times these blasts are released from the bone marrow and circulate in the blood stream and the white count can be very high. Patients will also be anemic, so their hemoglobins will be low. And generally speaking, the platelet count will also be low. So that's the first clue. And then the definitive test to diagnose acute myeloid leukemia is the bone marrow aspiration and biopsy. So this allows us to count the number of blasts, these early blood cells in the bone marrow, and by definition, if the blast count is 20% or more in either the bone marrow or the blood, we call this acute myeloid leukemia. So that's the first bit. And the second is that we want to, you hear advertisements all the time about personalized medicine. Well, that's exactly what we do in caring for patients with acute myeloid leukemia. So we want to learn as much about this person's disease as possible. And so we will also take specimens of the bone marrow and perform flow cytometry. What this does is allow us to, first of all, confirm the diagnosis of AML and differentiate it between the lymphoid leukemias. So that's important. And it can also help us determine the stage of differentiation of these cells. Then we will send cytogenetics. What this does is look at chromosomal abnormalities. Some of these are associated with better risk disease and some with harder to treat disease still can be curable, but generally tougher to treat. And same thing, we will send this sample for next generation sequencing. And this will allow us to look for genes that are commonly mutated in AML. And this can also be important in prognostication and determine the best treatment. And sometimes, in fact, we even have targeted drugs for these individualized point mutations that can occur. So these are the main tests we do on the bone marrow, aspirin, and biopsy to learn as much as we can about this individual's leukemia.