Relationship between the 46/1 haplotype of the JAK2 gene and the JAK2 mutational status and allele burden, the initial findings, and the survival of patients with myelofibrosis

Ann Hematol. 2014 May;93(5):797-802. doi: 10.1007/s00277-013-1989-5. Epub 2013 Dec 15.

Abstract

An association has been reported between a specific haplotype of the JAK2 gene, the homozygous 46/1 haplotype, and a predisposition to the development of chromosome Philadelphia-negative myeloproliferative neoplasms. Concerning myelofibrosis (MF), controversy remains on the relationship between the above JAK2 haplotype and the patients' clinicohematological features and survival. Among 132 patients with MF (60 % primary MF, 20 % postpolycythemia vera MF, 20 % post-essential thrombocythemia MF; 59 % JAK2V617F positive) who were analyzed for the JAK2 46/1 haplotype, 29 were found to be homozygous and 53 heterozygous. The homozygous 46/1 haplotype was more often observed in JAK2V617F-positive patients (29.5 versus 11 %, p = 0.012). Moreover, among JAK2V617F-positive patients, those who were homozygous for the 46/1 haplotype had a higher allele burden than the remainder (92 versus 48 %, p = 0.0017). Overall, patients with homozygous 46/1 haplotype showed significantly higher hemoglobin values and higher leukocyte counts, but no association was seen with other clinicohematological features. Finally, no relationship was observed between the JAK2 46/1 haplotype and either the patients' prognostic score or survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles*
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes*
  • Hemoglobins / metabolism
  • Heterozygote
  • Homozygote
  • Humans
  • Janus Kinase 2 / genetics*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Polycythemia Vera / complications
  • Polycythemia Vera / diagnosis
  • Polycythemia Vera / genetics*
  • Polycythemia Vera / mortality
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / etiology
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / mortality
  • Survival Analysis
  • Thrombocythemia, Essential / complications
  • Thrombocythemia, Essential / diagnosis
  • Thrombocythemia, Essential / genetics*
  • Thrombocythemia, Essential / mortality

Substances

  • Hemoglobins
  • JAK2 protein, human
  • Janus Kinase 2