title: Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia.
abstract: 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.
authors: Department of Hematology, University of Florence, 50134 Florence, Italy. amvannucchi@unifi.it
authors: Alessandro M
authors: AM
authors: Vannucchi
authors: Elisabetta
authors: E
authors: Antonioli
authors: Paola
authors: P
authors: Guglielmelli
authors: Alessandro
authors: A
authors: Rambaldi
authors: Giovanni
authors: G
authors: Barosi
authors: Roberto
authors: R
authors: Marchioli
authors: Rosa Maria
authors: RM
authors: Marfisi
authors: Guido
authors: G
authors: Finazzi
authors: Vittoria
authors: V
authors: Guerini
authors: Fabrizio
authors: F
authors: Fabris
authors: Maria Luigia
authors: ML
authors: Randi
authors: Valerio
authors: V
authors: De Stefano
authors: Sabrina
authors: S
authors: Caberlon
authors: Agostino
authors: A
authors: Tafuri
authors: Marco
authors: M
authors: Ruggeri
authors: Giorgina
authors: G
authors: Specchia
authors: Vincenzo
authors: V
authors: Liso
authors: Edoardo
authors: E
authors: Rossi
authors: Enrico
authors: E
authors: Pogliani
authors: Luigi
authors: L
authors: Gugliotta
authors: Alberto
authors: A
authors: Bosi
authors: Tiziano
authors: T
authors: Barbui
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005260:Female; D006400:Hematocrit; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009929:Organ Size; D011087:Polycythemia Vera / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000473:pathology; D011537:Pruritus / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D013154:Spleen / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000473:pathology; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2