Acquiring an MPN: Is There a Familial Predisposition?

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Is acquiring a myeloproliferative neoplasm (MPN) a family affair? What are the hereditary risks? Dedicated MPN researcher Dr. Angela Fleischman from UC Irvine discusses advances in understanding the disease course of an MPN, developing genetic mutations, and identifying the inherited risk for families. Dr. Fleischman also shares how relatives who are MPN patients can get involved with current research and gives recommendations on what testing family members can undergo. Watch now to hear her expert knowledge on inherited risk.

This is an MPN Research Foundation program produced by Patient Power. We thank Incyte Corporation for their support.

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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:          

So, Dr. Fleischman, you’ve got a lab too. 

Dr. Fleischman:           

Yes.

Andrew Schorr:          

So what’s your special interest there, whether or not you presented at ASH, where you’re hoping to move something along as well in maybe a different approach? 

Dr. Fleischman:           

So my primary focus is I’d like to figure out what underlies the predisposition to acquire an MPN, because I’m very struck by how it runs in families. It’s just very interesting to me that there can be families where multiple people have all acquired the same mutation. They were not born with a mutation, but they’ve acquired the mutation, so there must be something different about these families that when they have a cell that acquires the JAK2 mutation or calreticulin mutation, that cell does very well in their body.

I’m also struck that MPN patients, we know that they have a lot of inflammation. Also MPN patients and their family members are more likely to have autoimmune diseases which are inflammatory diseases. And so one thing that my lab is working on is whether a situation of chronic inflammation could promote the expansion of mutant cells. 

Where I would see going forward in the long run is trying to identify people who would be at risk of developing an MPN and trying to reduce inflammation in them so as to reduce their likelihood of developing an MPN. My lab focuses on the ways that MPN cells respond to inflammation differently than normal cells, as well as we look at the immune systems of MPN patients, as well as their family members, and are investigating how the MPN patient and family member’s immune system is different than people without MPN. 

Andrew Schorr:          

Sounds like if people have MPNs that run in their family, you’d like to hear from them. 

Dr. Fleischman:           

Yes, I would very much so. 

Andrew Schorr:          

Well, we’ve gotten some questions. Sheldon wrote in and he says, “If JAK2 is an acquired mutation, why then is there a higher frequency among people of Eastern European descent, for example, Ashkenazic Jews?” Dr. Fleischman, do you have a comment on that?

Dr. Fleischman:           

So that’s getting to the predisposition to acquire an MPN. There have been multiple groups who have looked to see whether variations—not necessarily mutations, but variations—in different areas of people’s DNA would predispose somebody to acquire an MPN. Certain genes have been identified to be increased—or specific variations have been identified to be increased in patients with MPN.

Interestingly, there’s a—they’re called SNPS, single nucleotide polymorphisms—actually on the JAK2 gene itself labeled as 46-1—where it’s very strongly associated with the JAK2 mutation, so if you have a JAK2 mutation, it’s likely on that DNA that has the 46-1 allele. 46-1 allele is very common in people. About 50 percent of people have this 46-1 allele, so it’s clear that not everybody who has this allele will go on to get a myeloproliferative neoplasm. Other SNPs have been identified in other genes; interestingly in a gene that’s associated with telomerase and other genes that we don’t quite know what their association with MPNs are. 

Andrew Schorr:          

So I’m Ashkenazic Jewish, and I know some other people—I know a number of people, of course, with myelofibrosis and other related conditions; some are Jewish, some are not. 

Some of are of Eastern European heritage, some are not. But is there some higher incidence, I guess is what Sheldon’s getting, something we’ve done in our Ashkenazic Jewish community or intermarriage, whatever, that has created this weakness, if you will? Anything identified that we know of yet?

Dr. Fleischman:           

There’s nothing been identified, per se, specifically in the Ashkenazi Jewish population. This is the area that I’d really like to focus is trying to figure out what it is that predisposes people to acquire—when they get a JAK2 mutant cell, why it does so well in their body and expands. 

Another interesting phenomenon that’s now being identified in normal aging people is, as people age, a good fraction of people will have blood cells that have mutations, for example, TET2, which can also be seen in MPN patients, so basically mutant cells in their blood, but their CBC, their blood counts are normal, and they don’t have any blood disorder, but yet they have cells in their body that have mutations. A less frequent mutation that normal people can have is actually JAK2V617F. 

That’s another interesting phenomenon that we’re just beginning to learn about is that a feature of potentially normal healthy aging is do develop blood cells with mutations that we currently only associate with blood cancers. 

Andrew Schorr:          

Dr. Fleischman, you’re gonna love this one. This is from Donna. Donna wrote in and says, “My sister and I were diagnosed with PVJAK two and three years ago. Our mother was diagnosed last year with ET CALR positive. Are there any clinical trials for familial MPNs, or is there any genetic counseling that’s recommended?” So first of all, they should get in touch with you.

Dr. Fleischman:           

Yes, please get in touch with me. I hope they live in California, but if not, we could try to get their blood another way. But this is just a great example of how it runs in families. It’s really amazing, when I talk to patients, how many patients will have family members with MPNs. Sometimes they won’t even know it would be MPN. They say, “Well, my dad, he needed phlebotomies,” or, “My grandpa always was getting his blood drawn,” and didn’t really know why and don’t necessarily associate it with the word MPN, but just knew that there was some blood condition. In terms of genetic counseling, there’s really no defined suggestions for what to do. What I usually tell patients is they’ll say, “Should my children go get tested?” They probably not necessarily need to be tested for the JAK2 mutation, but if they had an abnormal blood count, it would be important to tell their doctor that, “My mom or my dad or my sister or brother has PV or ET.” For example, if their platelets were a little high, it would important to mention, “Somebody in my family has ET.” Also if they have any signs or symptoms of a blood clot, that would be important to be evaluated sooner rather than later. 

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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Page last updated on April 11, 2018