Differential expression of JAK2 and Src kinase genes in response to hydroxyurea treatment in polycythemia vera and essential thrombocythemia

Ann Hematol. 2011 Aug;90(8):939-46. doi: 10.1007/s00277-011-1179-2. Epub 2011 Feb 18.

Abstract

This study investigates the differential gene expression profile of JAK2(V617F)-positive myeloproliferative neoplasm (MPN) patients, with and without response to hydroxyurea (HU) treatment. Twenty-one polycythemia vera, 28 essential thrombocythemia, eight secondary erythrocytosis, and 30 controls were studied. Thirty-four genes were overexpressed in patients who did not respond to HU. Of these, some participate in proliferative pathways: MAPK, AKT, Src kinase (SFK), and JAK2 pathway. JAK2 allele burden was similar between groups of responders and nonresponder. A molecular fingerprint distinguishes JAK2(V617F)-positive MPN patients without response to HU treatment, with overexpression of JAK2, MAPK14, PIK3CA, and SFK genes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hydroxyurea / pharmacology*
  • Hydroxyurea / therapeutic use
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Polycythemia / drug therapy
  • Polycythemia / genetics
  • Polycythemia Vera / drug therapy*
  • Polycythemia Vera / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / genetics
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Young Adult
  • src-Family Kinases / genetics*

Substances

  • Transcription Factors
  • JAK2 protein, human
  • Janus Kinase 2
  • src-Family Kinases
  • Hydroxyurea