title: Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele.
abstract: A total of 186 patients with primary myelofibrosis (PMF) were genotyped for JAK2V617F at diagnosis aimed at analyzing the correlation of mutational status and mutated allele burden with outcome variables, including time to anemia, leukocytosis, leukopenia, thrombocytopenia, massive splenomegaly, leukemia, and with overall survival. A total of 127 JAK2V617F-mutated patients (68% of whole series) were divided in quartiles of V617F allele burden. After a median follow-up of 17.2 months, 23 patients died, 15 because of leukemia. A JAK2V617F mutated status did not impact on the rate of leukemia transformation or overall survival. Patients in the lower quartile had shorter time to anemia and leukopenia and did not progress to large splenomegaly. Furthermore, survival was significantly reduced in the lower quartile compared with upper quartiles and JAK2 wild-type patients. In multivariate analysis, factors associated with reduced survival were age, a blast count more than 1%, and a JAK2V617F burden within first quartile. Causes of death in the lower quartile were represented mainly by systemic infections. We conclude that a low JAK2V617F allele burden at diagnosis is preferentially associated with a myelodepletive rather than myeloproliferative phenotype and represents an independent factor associated with shortened survival in patients with PMF.
authors: Unità Funzionale di Ematologia, Dipartimento di Area Critica, Università di Firenze, and Istituto Toscano Tumori, Firenze, Italy.
authors: Paola
authors: P
authors: Guglielmelli
authors: Giovanni
authors: G
authors: Barosi
authors: Giorgina
authors: G
authors: Specchia
authors: Alessandro
authors: A
authors: Rambaldi
authors: Francesco
authors: F
authors: Lo Coco
authors: Elisabetta
authors: E
authors: Antonioli
authors: Lisa
authors: L
authors: Pieri
authors: Alessandro
authors: A
authors: Pancrazzi
authors: Vanessa
authors: V
authors: Ponziani
authors: Federica
authors: F
authors: Delaini
authors: Giovanni
authors: G
authors: Longo
authors: Emanuele
authors: E
authors: Ammatuna
authors: Vincenzo
authors: V
authors: Liso
authors: Alberto
authors: A
authors: Bosi
authors: Tiziano
authors: T
authors: Barbui
authors: Alessandro M
authors: AM
authors: Vannucchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010649:Phenylalanine / Q000235:genetics; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D016019:Survival Analysis; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D010649:Phenylalanine; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D014633:Valine