Understanding Myelodysplastic Syndrome: Molecular Mechanisms and Diagnosis


Michael Savona, MD and Amer Zeidan, MBBS review the biology underlying myelodysplastic syndrome and explain the patient journey from symptom presentation to official diagnosis.

Dr. Michael Savona: Hello, and thank you for joining this Targeted Oncology discussion entitled The Evolving Treatment of Lower Risk MDS. Joining me today is my good friend and colleague from Yale University, Amer Zeidan. Amer?

Dr. Amer Zeidan: Thank you, Mike. It's a pleasure to be here with you today.

Dr. Michael Savona: Real good to have you. Thanks for joining me. Let's just level set by talking a little bit about what MDS is. So, myelodysplastic syndromes are actually a series of many different diseases in the bone marrow, starting with usually mutations within the hematopoietic stem cell that are passed down to those progeny cells and ultimately lead to a crowding of the marrow with premature cell types and the inability of those premature cell types to turn into the finished product. I often tell patients it's a bit like an auto factory with a bunch of chassis without wheels or windshields on them. And we think of MDS being a, as a matter of fact, many years ago it was called pre-leukemia. We think it as a precursor stage, but really only about a third to 40% of patients with MDS develop leukemia. Most patients with MDS develop progressive cytopenias, which ultimately lead to complications. For example, if their platelets are well, they bleed, if their hemoglobin goes low, they can have insufficiency infarcts of a variety of organs. And if their neutrophils are low, they develop neutropenic fever. Typically patients are diagnosed with low risk and they have a more indolent course. But sometimes we have patients who are fine one day and the next day they come in and they have no cell counts, and they already have quite a few blasts in their marrow are actually diagnosed with a disease which is much more likely to turn to leukemia quicker. And the treatment for that is a little different. Today we're going to talk mostly about lower risk MDS and those patients most commonly present with anemia, fatigue, often patients are found to have anemia after they complain of fatigue to their internists. And when anemia is found, if that anemia is normocytic and the patient has normal B12 folate and copper and iron, the next step is to look in the bone marrow. And in the bone marrow, we see dysplastic forms and recurrence cytogenetic and molecular abnormalities that tell us this is the disease that we're dealing this. Maybe you can talk a little bit more about how the disease is diagnosed more specifically, Amer.

Dr. Amer Zeidan: Yeah, and I think, as you alluded, MDS is quite interesting in the sense that the patients can really present with a very wide array of completely no symptoms just being picked up on a physical exam labs being done by primary care or pre-operative evaluation where the patient has no symptoms whatsoever. All the way to a presentation that's I can to acute myeloid leukemia, where all the blood counts are very low and the patient is very sick and they need to be treated in the hospital. At the same time, the management also very significantly, and we're going to talk about this later, but it could go all the way from just observing the patient to recommending bone marrow transplantation from the first visit. So it's a very wide spectrum, which reflects a significant, I think, variation in biology. The diagnostic process, as you mentioned, still heavily relies on a bone marrow biopsy although I think, very exciting data is evolving over the last few years about correlation between genetic abnormalities that are picked up in the blood and cytopenias. And we might be able to diagnose in the future MDS without necessarily doing a bone marrow, but the standard continues to be at this point is to do a bone marrow biopsy.

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