Myeloproliferative diseases are a group of bone marrow diseases characterized by excess production of cells. One of the diseases in this group, human polycythemia vera (PV), is associated in a majority of cases with mutations in the JAK2 signaling protein. In order to better understand the effects of these mutations on hematopoietic stem and progenitor cells in myeloproliferative disease, HSCI Principal Faculty member Benjamin Ebert, MD, and colleagues have described a mouse model with a JAK2 mutation that resembles PV. They find that the mutation in these mice has distinctly different effects on the hematopoietic stem cell compartment and the myeloid progenitor populations. Further, the researchers found that treating mice with an inhibitor of the mutant kinase removed the disease phenotype but did not remove the disease initiating cells. These results suggest that the disease cells may not be targeted by the kinase inhibitor and normal and mutant stem cells may have different molecular networks, with the JAK2 mutation not necessarily being the disease-initiating mutation. These findings have exciting implications for therapeutic approaches toward these types of bone marrow diseases and shed light on the role of JAK2 in HSC differentiation and function.

Mullally, A., Lane, S.W., Ball, B., Megerdichian, C., Okabe, R., Al-Shahrour, F., Paktinat, M., Haydu, J.E., Housman, E., Lord, A.M., Wernig, G., Kharas, M.G., Mercher, T., Kutok, J.L., Gilliland, D.G., Ebert, B.L. (2010). Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 17, 584-96.