title: Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden.
abstract: The aim of this study was to determine whether the burden of JAK2(V617F) allele correlated with major clinical outcomes in patients with polycythemia vera (PV). To this end, we determined JAK2 mutant allele levels in granulocytes of 173 PV patients at diagnosis. The mean (+/-s.d.) mutant allele burden was 52% (+/-29); 32 patients (18%) had greater than 75% mutant allele. The burden of JAK2(V617F) allele correlated with measurements of stimulated erythropoiesis (higher hematocrit, lower mean cell volume, serum ferritin and erythropoietin levels) and myelopoiesis (higher white cell count, neutrophil count and serum lactate dehydrogenase) and with markers of neutrophil activation (elevated leukocyte alkaline phosphatase and PRV-1 expression). As compared to those with less than 25% mutant allele, patients harboring greater than 75% JAK2(V617F) allele were at higher relative risk (RR) of presenting larger spleen (RR 4.7; P<0.001) or suffering from pruritus (RR 3.1; P<0.001). In these patients, the risk of requiring chemotherapy (RR 1.8; P=0.001) or developing major cardiovascular events (RR 7.1; P=0.003) during follow up were significantly increased. We conclude that a burden of JAK2(V617F) allele greater than 75% at diagnosis points to PV patients with high-risk disease.
authors.affiliation: Department of Hematology, University of Florence, Florence, Italy. amvannucchi@unifi.it
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: E
authors.initials: E
authors.lastname: Antonioli
authors.forename: P
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: G
authors.initials: G
authors.lastname: Longo
authors.forename: A
authors.initials: A
authors.lastname: Pancrazzi
authors.forename: V
authors.initials: V
authors.lastname: Ponziani
authors.forename: C
authors.initials: C
authors.lastname: Bogani
authors.forename: P R
authors.initials: PR
authors.lastname: Ferrini
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
authors.forename: V
authors.initials: V
authors.lastname: Guerini
authors.forename: A
authors.initials: A
authors.lastname: Bosi
authors.forename: T
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002318:Cardiovascular Diseases / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011087:Polycythemia Vera / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011537:Pruritus / Q000453:epidemiology; D012307:Risk Factors; D013163:Splenomegaly / Q000453:epidemiology; D013927:Thrombosis / Q000453:epidemiology
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2