Leukemia research
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The acquired recurrent mutation, JAK2 V617F, is the most frequent mutation associated with myeloproliferative neoplasms (MPNs). JAK2 signaling is critical in normal hematopoiesis. Studies using genetically engineered mouse models demonstrated a central role of JAK2 V617F in the pathogenesis of MPNs. ⋯ Clinical trials demonstrated that JAK1/2 inhibitors ameliorate constitutional symptoms and reduce spleen size in patients with myelofibrosis. However, JAK2 inhibitors have limited ability to reduce JAK2 V617F allele burden or bone marrow fibrosis in humans. JAK2 inhibitor-based combination therapies are being explored.