IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms

Leukemia. 2010 Jun;24(6):1146-51. doi: 10.1038/leu.2010.77. Epub 2010 Apr 22.

Abstract

Bone marrow DNA was screened for isocitrate dehydrogenase (IDH) mutations in 200 patients with chronic (n=166) or blast (n=34) phase myeloproliferative neoplasms (MPN). Included among the former were 77 patients with primary myelofibrosis (PMF), 47 essential thrombocythemia and 38 polycythemia vera (PV). Nine IDH mutations (5 IDH1 and 4 IDH2) were detected; mutational frequencies were approximately 21% (7 of 34) for blast-phase MPN and approximately 4% (3 of 77) for PMF. IDH mutations were seen in only 1 of 12 paired chronic-blast-phase samples and in none of 27 concurrently studied acute myeloid leukemia (AML) patients without antecedent MPN. IDH1 mutations included R132C (n=4; two post-PMF AML, one post-PV AML and one PMF) and R132S (n=1; post-PMF AML). IDH2 mutations included R140Q (n=3; one post-PMF AML, one post-PV AML and one PMF) and a novel R140W (n=1; mutation found in both chronic- and blast-phase samples). The entire study cohort was also screened for JAK2 and MPL mutations and JAK2V617F was found in three IDH-mutated cases (two PMF and one PV). This study shows a relatively high incidence of IDH mutations in blast-phase MPN, regardless of JAK2 mutational status, and the occurrence of similar mutations in chronic-phase PMF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blast Crisis / genetics*
  • Blast Crisis / pathology
  • Bone Marrow
  • Chronic Disease
  • Cohort Studies
  • Female
  • Genotype
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Janus Kinase 2 / genetics
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Receptors, Thrombopoietin / genetics

Substances

  • Receptors, Thrombopoietin
  • MPL protein, human
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Janus Kinase 2