TY - JOUR
T1 - Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia
AU - Vannucchi, Alessandro M.
AU - Antonioli, Elisabetta
AU - Guglielmelli, Paola
AU - Rambaldi, Alessandro
AU - Barosi, Giovanni
AU - Marchioli, Roberto
AU - Marfisi, Rosa Maria
AU - Finazzi, Guido
AU - Guerini, Vittoria
AU - Fabris, Fabrizio
AU - Randi, Maria Luigia
AU - De Stefano, Valerio
AU - Caberlon, Sabrina
AU - Tafuri, Agostino
AU - Ruggeri, Marco
AU - Specchia, Giorgina
AU - Liso, Vincenzo
AU - Rossi, Edoardo
AU - Pogliani, Enrico
AU - Gugliotta, Luigi
AU - Bosi, Alberto
AU - Barbui, Tiziano
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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 617V7gt;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.
AB - 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 617V7gt;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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U2 - 10.1182/blood-2006-12-064287
DO - 10.1182/blood-2006-12-064287
M3 - Article
C2 - 17379742
AN - SCOPUS:34547953018
SN - 0006-4971
VL - 110
SP - 840
EP - 846
JO - Blood
JF - Blood
IS - 3
ER -