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Are There Still MPNs That Are Unclassified?

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Published on February 18, 2020

Key Takeaways

  • There’s a JAK2 mutation in part of a gene that can’t turn itself off called V617F mutation. It’s in 97% of people with PV, 30% of people with ET, 50% of people with MF.
  • The CALR mutation is found in 20% of people with ET and in 30% of people with MF.
  • Up to 20% of patients are triple-negative, meaning they don’t have any of those mutations. Then, doctors must look at their clonal driver.

Myeloproliferative neoplasm expert Dr. Catriona Jamieson, from the UC San Diego Moores Cancer Center, answers a patient question on whether there are still MPNs that are unclassified.

Watch as Dr. Jamieson explains the known genetic mutations in MPN patients, how researchers are uncovering mutational patterns that were previously unreported—and what it indicates for disease progression and treatment.

This is an MPN Research Foundation program produced by Patient Power. We thank Celgene for their financial support through grants to the MPN Research Foundation. These organizations have no editorial control, and the program is produced solely by Patient Power.

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Transcript | Are There Still MPNs That Are Unclassified?

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Greetings, I'm Andrew Schorr. We're in Orlando, Florida and this is our live MPN Ask the Expert program. And I've been living with an MPN about eight years now, so I am vitally interested. now let's take your questions as well. So, joining us is my doctor, Dr. Catriona Jamieson. Thank you so much for being with us.

Dr. Jamieson:              

Oh, it's really my pleasure, Andrew.                       

Andrew Schorr:

I think Brenda asked this question, "Are there still MPNs that are unclassified?" So, we have ET, PV, MPN. She says, "Is there something that's not wild type," And you can tell us what that is, as you have with next-generation sequencing?" Is there something we've never given a name to?

Dr. Jamieson:              

Absolutely. So, myelo—it's hard to even say the word. "Myelo" means bone marrow. "Proliferative" means you have cells in the bone marrow that are making more of themselves. Neoplasm suggests it is a cancer, because it can progress to acute myeloid leukemia, AML for short. That was something that we didn't even have a mutation for until 2005 when four groups said there's a JAK2 mutation in part of the gene where it can't turn itself off. And that's a V617F mutation.

So, then we said, "Okay. That's 97.5 percent of people with polycythemia vera. About 30 percent of people with essential thrombocythemia. About 50 percent of people with myelofibrosis." But we didn't know about any other mutations. And then a few years later the CALR mutation was found. "Okay, now we've got about 20 percent of ET, another 30 percent of myelofibrosis."  

But there's still a proportion of patients where we can't find a mutation—or the bona fide mutations that we know as driver mutations. Where we think they're responsible for initiating the fibrosis and driving it, and making it get worse. And so, that is a proportion of patients that we're still trying to understand. But I think we're starting to make inroads based on next-generation sequencing, where we can see some mutational patterns that weren't previously reported. 

And I think what's happening are two things. One, people can inherit an inability for their immune system to see these clones as foreign. And number two, they get a mutation in a gene, that's what's called an epigenetic modifier. Like TET2 that you've heard about, DNMT3a, but they may not have that JAK2 mutation, or the calreticulin mutation, or the MPL mutation. Those are the three known mutations that drive this disease, but, you know, we've got 20 – up to 20 percent of patients who are triple-negative. They don't have any of those mutations. 

Andrew Schorr:                      

So, how do you treat it?

Dr. Jamieson:              

So, then we look at what is their clonal driver? Or what is the clone in the background? And we looked for the very same things. Do they have scarring in the bone marrow? Do they have a bigger spleen? And so, we start with the same recommendations for that group, but we tend to be a little bit more discerning about signs of progression, because it tends to be a more aggressive group. 

They tend to progress more quickly. So, what we're looking at is a mutation and has international prognostic scoring system maps 70. For people under 70 to say, "Is there a subgroup of patients we should think of transplanting earlier?" So, people with the ASXL1 mutation, IDH-1 or -2 mutation, TET2. Is that a group we should start to look at more carefully?

Andrew Schorr:             

And that would be the treatment. 

Dr. Jamieson:              

And that could be the treatment, or we may start to get a little bit clever about the type of cellular therapy we give people, recognizing the immune system is not recognizing these pre-malignant or malignant clones as foreign, and giving people NK cells, natural killer cells, or targeted T cells  that recognize these new proteins on the surface of these cells. And those clinical trials are going on.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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