[Recent advances in molecular pathogenesis of myeloproliferative neoplasms].

Myeloproliferative neoplasms (MPNs) are characterized by activation of the JAK-STAT pathway due to driver mutations including JAK2V617F and MPLW515K/L, as well as to mutations in CALR. Driver mutations phosphorylate multiple STAT proteins that lead to proliferations, differentiations and cytokine secretions of various hematopoietic cells. However, hematopoietic cells carrying JAK2V617F, which causes excessive cellular proliferation and differentiation, do not necessarily have a clonal growth advantage in terms of hematopoietic repopulation. Alterations of epigenetic modifiers involving histone modifications and DNA methylations, which often co-exist with driver mutations and eventually upregulate several oncogenes, may play crucial roles in long-term clinical courses characterized by progression to myelofibrosis or acute leukemia in MPNs. In addition to JAK2 inhibition, molecules altered by abnormal epigenetic modifications may be worth exploring as potential new therapeutic targets in MPNs.