Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia.
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.
Vannucchi
Alessandro M
AM
Department of Hematology, University of Florence, 50134 Florence, Italy. amvannucchi@unifi.it
Antonioli
Elisabetta
E
Guglielmelli
Paola
P
Rambaldi
Alessandro
A
Barosi
Giovanni
G
Marchioli
Roberto
R
Marfisi
Rosa Maria
RM
Finazzi
Guido
G
Guerini
Vittoria
V
Fabris
Fabrizio
F
Randi
Maria Luigia
ML
De Stefano
Valerio
V
Caberlon
Sabrina
S
Tafuri
Agostino
A
Ruggeri
Marco
M
Specchia
Giorgina
G
Liso
Vincenzo
V
Rossi
Edoardo
E
Pogliani
Enrico
E
Gugliotta
Luigi
L
Bosi
Alberto
A
Barbui
Tiziano
T
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
C507924:JAK2 protein, human; D053614:Janus Kinase 2