Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia.

JAK2(V617F) mutation occurs in an homozygous status in 25-30% of patients with polycythemia vera (PV) and 2-4% with essential thrombocythemia (ET). Whether homozygosity associates with distinct clinical phenotypes is still under debate. This retrospective multicentric study considered 118 JAK2(V617F) homozygous patients (104 PV, 14 ET) whose clinical characteristics were compared to those of 587 heterozygous and 257 wild-type patients. Irrespectively of their clinical diagnosis, homozygous were older, displayed higher leukocyte count and hematocrit value at diagnosis, and presented larger spleen volume. Aquagenic pruritus was significantly more common among homozygous PV patients. JAK2(V617F) homozygosity associated to more frequent evolution into secondary myelofibrosis in both PV and ET. After adjustement for gender, age, leukocytes and previous thrombosis in a multivariate analysis, homozygous ET patients displayed a significantly higher risk of cardiovascular events (HR 3.97, CI 95% 1.34-11.7; p=0.013) than wild-type (HR=1.0) or heterozygous (HR=1.49). No significant association of JAK2(V617F) homozygosity with thrombosis risk was observed in PV. Finally, JAK2(V617F) homozygous patients were more likely to receive chemotherapy for control of disease. We conclude that JAK2(V617F) homozygosity identifies PV or ET patients with a more symptomatic myeloproliferative disorder and is associated with a higher risk of major cardiovascular events in patients with ET.