Isocitrate dehydrogenase mutations in leukemia

J Clin Invest. 2013 Sep;123(9):3672-7. doi: 10.1172/JCI67266. Epub 2013 Sep 3.


Recent genome-wide discovery studies have identified a spectrum of mutations in different malignancies and have led to the elucidation of novel pathways that contribute to oncogenic transformation. The discovery of mutations in the genes encoding isocitrate dehydrogenase (IDH) has uncovered a critical role for altered metabolism in oncogenesis, and the neomorphic, oncogenic function of IDH mutations affects several epigenetic and gene regulatory pathways. Here we discuss the relevance of IDH mutations to leukemia pathogenesis, therapy, and outcome and how mutations in IDH1 and IDH2 affect the leukemia epigenome, hematopoietic differentiation, and clinical outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • DNA Mutational Analysis
  • DNA-Binding Proteins / metabolism
  • Glutarates / metabolism
  • Humans
  • Isocitrate Dehydrogenase / antagonists & inhibitors
  • Isocitrate Dehydrogenase / genetics*
  • Leukemia / drug therapy
  • Leukemia / enzymology
  • Leukemia / genetics*
  • Molecular Targeted Therapy
  • Mutation, Missense*
  • Proto-Oncogene Proteins / metabolism


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Glutarates
  • Proto-Oncogene Proteins
  • TET2 protein, human
  • alpha-hydroxyglutarate
  • Isocitrate Dehydrogenase
  • isocitrate dehydrogenase 2, human
  • IDH1 protein, human