How do molecular test results affect care for people with myelodysplastic syndrome (MDS)? Dr. Singh explains how identifying genetic mutations such as IDH1, IDH2, and TET2 can help doctors personalize care, guide treatment decisions, and track disease progression over time.
Dr. Abhay Singh is a physician specializing in acute and chronic leukemias at Cleveland Clinic and serves as Assistant Professor of Medicine at the Lerner College of Medicine of Case Western Reserve University. Learn more about Dr. Singh.
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Transcript
Jamie Forward:
So, let’s talk a little bit more about molecular testing. So, you mentioned next-generation sequencing. So, Dr. Singh, can you define this molecular testing and share how it’s impacting the field of cancer care?
Dr. Abhay Singh:
Yes. So, all of us have a gene makeup, which is pretty similar, but there are slight changes. And it’s a very structured order. So, there’s letters that go from one direction to the other. And then sometimes what can happen is through the process of aging, the most common cause, those sequences can get altered. And when those sequences get altered, those are called mutations. And then, those mutations lead to the production of defective proteins, so to speak.
So, that either can halt cellular maturation or they won’t let mature cells to grow. Or what it can make is make abnormal cells or dysplastic cells, the very hallmark of myelodysplastic syndrome. So, molecular testing gives us an opportunity to look at that point mutation or a point defect in that sequence.
So, what the next-generation sequencing means is that we are able to line up the sequence that’s there in an MDS patient with a normal sequence. And if there are any alterations that are identified, they can be identified in a particular gene and that gene may be IDH1, that gene may be IDH2, that gene may be TET2.
So, we know that that’s where the sequence defect is. And if we target that sequence defect, we can make that either abnormal protein to go away or alter that sequence so that those altered sequence cells die, but the normal cells thrive, and then we can let the normal maturation to take place again.
So, that’s why it is very important to get have that testing done because that 1.) it gives us a lot of therapeutic options, obviously, clinical trials, but 2.) because now we have risk stratification models that are much more advanced than the previous ones where we can put in the type of mutation, the number of mutations, the size of mutations, and that can help us better understand if it’s a high-risk disease or a low-risk disease because low-risk disease and high-risk diseases are very different and the treatment options are very varied as well as we discussed before.
Jamie Forward:
Okay, that’s very interesting. So, Dr. Singh, you mentioned that patients should undergo molecular testing at diagnosis. Is there a reason to do molecular testing later, maybe after treatment, or where does that fit in? At what point should they undergo molecular testing?
Dr. Abhay Singh:
Yeah, so there is no consensus guidelines or written protocols around it, but within the field, we strongly believe that anytime you’re suspecting that disease is progressing or it’s losing the response, one should repeat a molecular testing because oftentimes what we can see is that there is a new mutation that gets acquired, and let’s say that mutation, if it’s a targetable one, you have a potential drug that can be used in the later line. However, if we don’t repeat that testing and we run out of treatment options, then we don’t have a lot of things to consider.
So, I would say at the time of relapse, at the time of suspected progression, at the time of any planned bone marrow procedure, one should get a molecular testing done to see if the disease has evolved because MDS is an always evolving disease. Something’s happening.
So, you have to identify evolution and then act early.