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Vannucchi, Alessandro M.; Antonioli, Elisabetta; Guglielmelli, Paola; Rambaldi, Alessandro; Barosi, Giovanni; Marchioli, Roberto; Marfisi, Rosa Maria; Finazzi, Guido; Guerini, Vittoria; Fabris, Fabrizio; Randi, Maria Luigia; De Stefano, Valerio; Caberlon, Sabrina; Tafuri, Agostino; Ruggeri, Marco; Specchia, Giorgina; Liso, Vincenzo; Rossi, Edoardo; Pogliani, Enrico; Gugliotta, Luigi; Bosi, Alberto; Barbui, Tiziano
Blood, 08/2007, Volume: 110, Issue: 3Journal Article
JAK2 617V>F mutation occurs in a homozygous state in 25% to 30% of patients with polycythemia vera (PV) and 2% to 4% with essential thrombocythemia (ET). Whether homozygosity associates with distinct clinical phenotypes is still under debate. This retrospective multicenter study considered 118 JAK2 617V>F homozygous patients (104 PV, 14 ET) whose clinical characteristics were compared with those of 587 heterozygous and 257 wild-type patients. Irrespective of their clinical diagnosis, homozygous patients were older, displayed a higher leukocyte count and hematocrit value at diagnosis, and presented larger spleen volume. Aquagenic pruritus was significantly more common among homozygous PV patients. JAK2 617V>F homozygosity associated with more frequent evolution into secondary myelofibrosis in both PV and ET. After adjustment for sex, age, leukocyte count, and previous thrombosis in a multivariate analysis, homozygous ET patients displayed a significantly higher risk of cardiovascular events (hazard ratio HR 3.97, 95% confidence interval CI 1.34–11.7; P = .013) than wild-type (HR = 1.0) or heterozygous patients (HR = 1.49). No significant association of JAK2 617V>F homozygosity with thrombosis risk was observed in PV. Finally, JAK2 617V>F homozygous patients were more likely to receive chemotherapy for control of disease. We conclude that JAK2 617V>F 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.
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