Dr. Angela Fleischman has been researching the familial prevalence of MPNs for nearly ten years. A faculty member at the University of California Irvine, she hopes to one day be able to study patients remotely to expand her research outside of the Southern California area and broaden the scope of the MPN patient family registry. Dr. Fleischman earned her Ph.D. and MD from Stanford University and knew early on her goals of the research.
“I went to medical school for the purpose of focusing on hematologic malignancies and for the primary purpose of doing research and clinical care of blood cancers.” It was during her Ph.D. program that Dr. Fleischman found her passion for research. She says, “I started graduate school in a Ph.D. program in 1998 and found a lab that worked on blood stem cells and really just fell in love with blood cell production. I thought it was very interesting how blood stem cells decide to become one type of cell or another. That just really fascinated me. And then a year or two into my Ph.D. I realized that I needed to get a medical degree in order to be able to identify what the important questions were in blood cancers so I could then go back to the lab and find answers that would have an impact on patients.” And she has been identifying the important questions and is doing that research today, research that she hopes will change the course of disease progression and treatment of MPN patients in the future.
Why do the mutant cells gain the advantage over the good stem cells in MPN patients? This is one of the questions that propels Dr. Fleischman’s research. “In terms of cancer and blood conditions there is a big focus on getting rid of bad cells, and focusing only on them, but what I’d like to focus on is thinking about why those mutant cells in an MPN person gain the selective advantage over their normal cells and outcompete the normal cells.” She asks, “What sorts of pressures were put upon their blood stem cells that made mutant cells have the selective advantage?”
Dr. Fleischman’s work of focusing on maintaining the health of the normal cells so the mutant cells don’t gain the advantage would likely improve outcomes for patients in the early stages of the disease. By targeting early-stage disease, or even patients with no disease symptoms through lifestyle intervention, such as altering the diet or the introduction of supplements and antioxidants (that have no negative effect and pose no risk to the patient), nonpharmaceutical interventions have the potential to protect normal stem cells and get rid of the advantage of JAK2 mutant cells. “Maybe the mutant stem cells really aren’t the big problem, maybe the big problem is there is something going on with their normal stem cells, so these mutant cells now have a selective advantage…but if we could make normal cells perfect and healthy, maybe the mutant cells wouldn’t have a selective advantage and just go away.” She says.
Does an MPN patient play a valuable role in his or her outcomes? If asking Dr. Fleischman the answer is a resounding yes. “I think that we are probably underestimating the impact of lifestyle …the patient is an active participant and they have the power to alter their disease course. The current status of our healthcare system is you go to the Doctor and the Doctor gives you some sort of pill or drug to take care of your disease, but in reality, we are not really empowering the patient and thinking that they have control over and an impact on their health.” And Dr. Fleischman will attest she has anecdotally heard from patients who have put effort into changing their diet that they do in fact feel better and have more energy.
It’s also the familial prevalence that drives Dr. Fleischman’s research. “When you think about it, in these families (with multiple MPNs) they all have an outgrowth of a clone with the exact same mutation. Doesn’t that say to you that there’s something unique going on in these people? When they get a blood stem cell, with a JAK2 mutation, that cell has a selective advantage in those people and grows out.” She says. By identifying what’s in common with family members who have an MPN, and what features are present in those people, Doctor Fleischman believes researchers could better manipulate the evolution of the disease towards a more benign outcome. Furthermore, she acknowledges understanding why MPNs are prevalent in some families will have relevance to the patient with a sporadic MPN as well.
By creating a national registry of families affected by MPNs, Dr. Fleischman’s goal is not only to study the commonalities of affected family members but further to identify family members who are at risk or destined to develop MPNs in their lifetime and treat them early on, rather than current late-stage treatment. “I am very excited about trying to figure out ways to block progression of MPNs from the very beginning. At present time it’s very unsatisfying for most MPN patients and physicians in very early PV and ET stages to do nothing active about the progression of their disease…I’m excited about testing interventions that would actually change the natural history of the disease, and targeting people very early on during their disease. Currently, most efforts at intervention are restricted to late-stage disease. But it would be more ideal to intervene much earlier as to prevent the progression to MF or Leukemia. It seems to me early- stage disease is more impactful to do something about.” She says.
Looking toward the future, Dr. Fleischman sees her research focusing on preventative strategies to block progression for those with an early stage MPN such as PV or ET, and also to prevent the development of MPNs in high-risk populations, such as MPN family members. And in looking back, Dr. Fleischman is grateful to her mentors Dr. Mike Deininger who is now at The University of Utah and Drs. Brian Druker and Grover Bagby at Oregon Health & Science University.
If you are interested in finding out more about Dr. Fleischman’s lab or participating in research, please visit www.wearempn.org and www.mpnlab.org. If you believe MPNs could be prevalent in your family, Dr. Fleischman invites you to email her at agf@uci.edu or wearempn@gmail.com.
Contributed by Jennifer Acker