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

Leukemia. 2008 Apr;22(4):756-61. doi: 10.1038/sj.leu.2405097. Epub 2008 Jan 24.


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.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alleles
  • Bone Marrow Examination
  • Disease-Free Survival
  • Female
  • Gene Frequency
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Platelet Count
  • Primary Myelofibrosis / epidemiology
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / mortality*
  • Survival Rate


  • Janus Kinase 2