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IDH1/IDH2 Inhibition in Acute Myeloid Leukemia

Claudio Cerchione1, Alessandra Romano2, Naval Daver3

  • 1Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Frontiers in Oncology
|April 26, 2021
PubMed

Insights

Mutations in isocitrate dehydrogenases (IDH) 1 and 2 impact acute myeloid leukemia (AML) treatment. Targeted therapies like enasidenib and ivosidenib show promise in promoting AML cell differentiation and maturation.

Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Isocitrate dehydrogenases (IDH) 1 and 2 mutations are found in approximately 20% of acute myeloid leukemia (AML) patients.
  • These mutations play a role in leukemogenesis, driving cancer development.

Purpose of the Study:

  • To review the role of IDH1/IDH2 mutations in AML.
  • To highlight the progress of targeted therapeutics for AML patients with these mutations.

Main Methods:

  • Review of recent scientific literature and clinical trial data.
  • Analysis of biological and clinical properties of mutated IDH isoforms.

Main Results:

  • Targeting IDH mutations promotes differentiation and maturation of malignant AML cells.
  • Small molecule inhibitors enasidenib (targeting IDH1) and ivosidenib (targeting IDH2) have demonstrated safety, tolerability, and efficacy in Phase I/II trials.

Conclusions:

  • IDH1/IDH2 mutations represent a targetable vulnerability in AML.
  • Targeted therapies offer a promising individualized treatment strategy for AML patients with IDH mutations.
Keywords:
AMLIDHacute myeloid leukemiaenasidenibisocitrate dehydrogenaseivosidenibtarget therapy

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