title: Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival.
abstract: The clinical relevance of JAK2V617F allele burden in primary myelofibrosis (PMF) has not been previously studied. Bone marrow-derived DNA from 199 patients with PMF was subjected to qualitative (n=199) and quantitative (n=129) analysis for V617F. Mutational frequency was 58% and median mutant allele burden ratio in V617F-positive patients was 29% (range, 1-74%). Multivariable analysis identified older age, platelet count > or =100 x 10(9) l(-1) and peripheral blood blast percentage <3% as being associated with a positive mutational status. The mere presence of the mutation did not affect the incidence of thrombosis (P=0.78), overall survival (P=0.22) or leukemia-free survival (P=0.5). The 129 patients with allele burden information were divided into four groups: V617F-negative (n=53) and V617F-positive with mutant allele burden in the lower quartile (n=19), middle quartiles (n=38) or upper quartile (n=19) range. Kaplan-Meier plots revealed significantly shortened overall (P=0.0008) and leukemia-free (P=0.01) survival for the lower quartile, but not for upper quartile allele burden group; independent prognostic relevance was validated by multivariable analysis. We conclude that low V617F allele burden in PMF might indicate the presence of an overriding V617F-negative clone that confers a more aggressive disease phenotype.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA. tefferi.ayalew@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: T L
authors.initials: TL
authors.lastname: Lasho
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: Finke
authors.forename: R A
authors.initials: RA
authors.lastname: Mesa
authors.forename: C Y
authors.initials: CY
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001856:Bone Marrow Examination; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D053614:Janus Kinase 2