How can test results affect your MPN treatment options? Dr. Shivani Handa explains molecular testing for myeloproliferative neoplasms (MPNs) and the role certain genetic mutations play in prognosis and personalizing care decisions for people with essential thrombocytosis (ET), polycythemia vera (PV), and myelofibrosis (MF).
Dr. Shivani Handa is a hematologist-oncologist at the Ohio State University Comprehensive Cancer Center. Dr. Handa specializes in myeloid malignancies, which includes myeloproliferative neoplasms, myelodysplastic syndrome, and acute leukemias. Learn more about Dr. Handa.
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Transcript
Katherine Banwell:
Dr. Handa, what is molecular testing, and how do the results impact the care and treatment of people living with myeloproliferative neoplasms?
Dr. Shivani Handa:
So, molecular testing has become very essential in all cancers these days. So, there are two main parts to molecular testing.
So, we look at chromosomes, and we look at the DNA. The chromosome testing is called cytogenetics, and the DNA testing is referred to as next-generation sequencing where we look at different mutations.
So, there are three different driver mutations that are seen in over 95 percent of MPNs, that includes the JAK2V617F, the CALR or the calreticulin mutation, and the MPL or MPL mutation. And all of these drive the downstream signaling, the JAK-STAT pathway that essentially produces MPNs. And then besides these driver mutations, there are a ton of other mutations that we now know that have a significant prognostic impact on disease biology, so it’s essential that we test for these at diagnosis still to stratify patients.
And we have well-validated scoring systems these days like the MIPSS score that we can use to inform treatment decisions regarding where to send somebody for a bone marrow transplant and also predict their overall survival and their chance of progression to leukemia.
Katherine Banwell:
Dr. Handa, would you define targeted therapies for the audience and tell us how this type of treatment works?
Dr. Shivani Handa:
Yeah. So, targeted therapies are drugs that act very precisely at the driver mutation that’s driving the disease. So, with MPNs we have JAK inhibitors that are targeted therapies that are four different JAK inhibitors approved, and these all work on that JAK-STAT pathway that makes these cells more proliferative.
In addition to JAK inhibitors, we are also looking at targeted therapies for CALR or the calreticulin mutation, and this is really exciting for MPNs. And the CALR protein is being targeted through different mechanisms, so there’s a vaccine trial, there’s also a monoclonal antibody trial, there are T-cell redirecting approaches that are being looked at. So, lots to come in that space.