The role of IDH mutations in acute myeloid leukemia

Future Oncol. 2018 Apr;14(10):979-993. doi: 10.2217/fon-2017-0523. Epub 2018 Mar 15.

Abstract

Isocitrate dehydrogenases (IDHs) are enzymes involved in multiple metabolic and epigenetic cellular processes. Mutations in IDH1 or IDH2 are detected in approximately 20% of patients with acute myeloid leukemia (AML) and induce amino acid changes in conserved residues resulting in neomorphic enzymatic function and production of an oncometabolite, 2-hydroxyglutarate (R-2-HG). This leads to DNA hypermethylation, aberrant gene expression, cell proliferation and abnormal differentiation. IDH mutations diversely affect prognosis of patients with AML based on the location of the mutation and other co-occurring genomic abnormalities. Recently, novel therapies specifically targeting mutant IDH have opened new avenues of therapy for these patients. In the present review, we will provide an overview of the biological, clinical and therapeutic implications of IDH mutations in AML.

Keywords: AML; IDH1; IDH2; leukemia; therapy.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic
  • Glutarates / antagonists & inhibitors
  • Glutarates / metabolism
  • Humans
  • Isocitrate Dehydrogenase / antagonists & inhibitors*
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / therapy*
  • Mutation*
  • Prognosis

Substances

  • Antimetabolites, Antineoplastic
  • Enzyme Inhibitors
  • Glutarates
  • alpha-hydroxyglutarate
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human