My Father, Myelofibrosis, and Me

Ashley Gould with her father, Harvey

by Ashley Gould
Vice President Corporate Development & Chief Legal Officer, 23andMe

Linda Avey and Anne Wojcicki created 23andMe based on a number of visions. They described one of these to me in early 2007, capturing my imagination and playing a large role in my decision to become a member of the 23andMe team. This vision was of a web-based, patient-driven method of conducting research that removes physical boundaries and accelerates the search for answers. The company has already made this vision a reality by launching Parkinson’s and Sarcoma Communities with participant data streaming in daily from dedicated surveys.

I am privileged and excited to announce that 23andMe is launching a Myeloproliferative Neoplasms (MPN) Community for patients with polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (primary, post-PV and post-ET myelofibrosis), chronic myelogenous leukemia (CML), mastocytosis, and hypereosinophilic syndrome (HES) / related eosinophil disorders. This group of rare blood cancers affects production of blood cells in the bone marrow and has no known cure except for blood or marrow transplantation.

My father, Harvey Gould, is now in his 11th year living with a diagnosis of primary myelofibrosis (PMF), a type of MPN in which the bone marrow makes abnormal blood cells and is replaced by increasing amounts of fibrous scar tissue over time. He is one of a relatively small group of PMF patients in the United States. A study by the Mayo Clinic reported an incidence of 1.46 per 100,000 persons (1), and a prevalence of 30,000 patients nationwide. It’s also likely that some individuals don’t even know they have the disease because only highly trained specialists can diagnose it. The challenging nature of the disease, low incidence rate, and perhaps under-familiarity with the disease may partly explain why significant resources have not been applied towards identifying both inherited and acquired causes of myelofibrosis or towards development of effective therapies for this chronic and debilitating disease.

In 2005, several groups identified a mutation in the gene JAK2, referred to as JAK2 V617F in several MPNs. It is found in approximately 95% of patients with PV, and 50-60% of patients with ET and PMF.  The JAK2 protein is a signaling protein within cells; when JAK2 is mutated, it contributes to increased signaling in cells and abnormal cell proliferation, a hallmark of these blood cancers.  A number of clinical trials are now in progress with JAK inhibitors targeting the JAK2 protein and related signaling abnormalities in cells.  These trials, now mostly in patients with myelofibrosis, are listed at www.clinicaltrials.gov (search term “myelofibrosis” and “JAK2″). These investigational drugs have demonstrated substantial activity shrinking patient spleen size and improving symptoms. These JAK inhibitors have the potential to be the first major class of drugs approved for myelofibrosis. We’re looking to gather valuable information that might be helpful to researchers who are studying these diseases and inspire others to join in.

Ashley and Harvey Gould at Ashley's wedding

I know from following my father’s struggles that treating myelofibrosis is more of an art than a science, even with highly skilled physicians involved. For more than four years, the drug imatinib (Gleevec®) seemed to be helping, and then it simply stopped working. Why did it work at all when it does not work for most myelofibrosis patients? Why did it suddenly stop being effective?

A few years ago, while in Ireland, my father collapsed when his hemoglobin suddenly dropped from 13.4 g/dL (almost normal) to 5.4 g/dL (a crisis level). He received twelve units of blood on seven separate days over the course of three weeks, plus another two units after he was able to return to the States. This spurred my father to write to the Taoiseach (Irish Prime Minister), seeking recognition that he’d become a full-blooded Irishman — his Jewish heritage notwithstanding. (See his letter to the Taoiseach, correspondence from various offices in the Irish government, and the final verdict from the Tanaiste).

While my father’s gift for humor has helped us all cope, we still have many unanswered questions stemming from his experience.  If we knew more about the genetic components of the disease, would researchers be able to find causes and cures? Could doctors better anticipate the progression of the disease? Could doctors better tailor drugs to their patients? Responses to these questions remain unknown for many of the myeloproliferative neoplasms. It’s our search for answers that has lead to the formation of 23andMe’s MPN Community.

We are honored to welcome Drs. Jason Gotlib and James Zehnder from the Stanford University School of Medicine and Stanford Cancer Center, as expert advisors and research collaborators in this effort. Dr. Gotlib brings his experience in clinical hematology and leadership in numerous phase I/II trials of novel therapies for MPNs. Dr. Zehnder, Professor in the Division of Hematology and Department of Pathology, contributes expertise in the realm of MPN molecular diagnostics. Their complementary skill sets will be an asset to the 23andMe program and MPN research efforts.

Watch the video below to learn more about my father’s story and help by joining our research community.

Please note: 23andMe filmed this video when we planned to launch a more narrowly focused Myelofibrosis Community. Based upon valuable input from our scientific advisory team, 23andMe has since decided to expand the scope of our community to include all myeloproliferative neoplasms, including myelofibrosis (primary, post-PV, and post-ET myelofibrosis), polycythemia vera (PV), essential thrombocythemia (ET), CML, mastocytosis, as well as hypereosinophilic syndrome (HES) and related eosinophil disorders.

Our initial goal is to enroll approximately 1,000 patients diagnosed with a spectrum of myeloproliferative neoplasms who consent to participate in our research and who agree to complete surveys about their experiences. Patients will be asked to provide a sample of saliva (kits send to the patient’s address) to test their DNA for potential inherited predispositions to MPNs, and to assess whether the DNA results correlate with certain survey findings.  As our MPN Community page describes in more detail, participants will receive complimentary access to 23andMe’s full Personal Genome Service®. If you are someone who has been diagnosed with a myeloproliferative neoplasm, follow this link to learn more about joining our MPN Research Community and sign up. If you know someone who you think might meet the criteria, please share this information with them.

If you are not a patient with myelofibrosis or other MPN diagnosis, you can still help by becoming a 23andMe customer and opting in to participate in our 23andWe research program. Having genetic information for generally healthy individuals plays an important role in research as well. Everyone has the opportunity to participate and support research that can lead to new treatments and possible cures.

 (1) Mesa R, Silverstein M, Jacobson, Wollan P, Tefferi A.  Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted county study, 1976-1995.

Gleevec® is the trademark of Novartis Pharmaceuticals Corporation. 23andMe and Personal Genome Service are trademarks of 23andMe.