Mission and Goals
Myeloproliferative neoplasias (MPN or MPD) have been traditionally divided into two groups. Classic MPNs include:
- Essential thrombocythemia (ET)
- Polycythemia vera (PV)
- Primary myelofibrosis (PMF)
Atypical MPNs include:
- Juvenile myelomonocytic leukemia (JMML)
- Systemic mastocytosis (SM)
- Chronic Eosinophilic Leukemia/Hypereosinophilic Syndrome (HES)
Classic MPNs are characterized by overproduction of cells in the bone marrow leading to too many cells in the bloodstream. Currently, specific disease classification between the 3 classic MPN diagnoses is based on the predominant pattern of different cells present in blood and the presence or absence of reactive bone-marrow fibrosis (scar tissue in the bone marrow that develops as a reaction to the presence of bad cells). For example, in ET, platelets in blood are very high while other cell types are not, and the bone marrow shows no fibrosis.
The incidence of these diseases varies, from ~1.5 (for PMF) to ~2.3-2.5 (for ET and PV) per 100,000 people/year; this means that every year about 20.000 new patients are diagnosed with classic MPN. The total number of patients with MPN in the USA is probably about 250,000. The average age of patients at diagnosis is 60-65 years, but the diseases spare no age group. Life expectancy varies between classic MPN: decades for ET and PV, but only 5-7 years for PMF patients. A major problem with ET and PV, however, is increased risk of thrombosis and bleeding that may severely affect patients’ quality of life (e.g. heart attack or brain infarct). In addition, some patients with ET and PV transform to MF and their life expectancy is then much shorter, 5-7 years.
PMF is the most difficult among classic MPN as it typically includes worsening bone marrow fibrosis (scarring) with progressive lowering of blood cell counts requiring transfusions, massive enlargement of the spleen and liver, profound fatigue, weight loss, night sweats, and low-grade fever (very bad quality of life). Terrible body wasting and multi-organ failure eventually causes death.
Therapy for myeloproliferative neoplasias, and specifically PMF, is unsatisfactory. No medication is approved as a specific therapy for PMF. Many medications are used to help patients cope with body deterioration related to PMF but none have been shown to affect the inevitable outcome. Many clinical studies with novel medications are underway to find better therapies. New molecular abnormalities (e.g. mutation in a gene called JAK2) are being discovered in these diseases that are potential targets for drug development (e.g. JAK2 inhibitor might positively affect the disease and help the patients).
It is crucial that we identify treatment strategies to effectively treat MPN, providing clinical benefit for patients and prolonging their life expectancy, and ultimately curing them from the disease. The study of these relatively rare malignancies may provide insights for the treatment of more common medical problems. The knowledge about intracellular signaling and transduction pathways which result in an over abundance of immature red blood cells in PV, may help, for example, to devise medications to treat patients with potentially fatal anemia. Similarly, the ability to decrease platelet numbers in ET might lead to up regulation treatments for thrombocytopenia (more common problem of low platelet number in the blood) and end-stage leukemia. Therapies that would eliminate fibrosis in PMF may help patients with many other fibrotic diseases (e.g. lung fibrosis).