• What is IDH2?
  • IDH2 in Acute Myeloid Leukemia
  • Clinical Trials


Isocitrate dehydrogenase 2 (NADP+), mitochondrial (IDH2) is a gene that encodes an epigenetic modifier, a NADP(+)-dependent enzyme that is found in mitochondria (Gene 2013). Wild type IDH2 converts isocitrate to α-ketoglutarate, a step in the Krebs cycle, an important metabolic pathway that affects many other cellular biochemical processes (Shih et al. 2012).

IDH2 is frequently mutated in glioma, acute myeloid leukemia, and myelodysplastic syndromes (Haferlach et al. 2014; Walter et al. 2013; Yang et al. 2012). Mutations generally involve point mutations at the R140 and R172 residues of the protein. Mutations in IDH1 and IDH2 result in deleterious “gain of function”: instead of converting isocitrate to α-ketoglutarate, mutated IDH1 or IDH2 converts isocitrate to 2-hydroxyglutarate (Shih et al. 2012; Yang et al. 2012). 2-hydroxyglutarate inhibits other proteins involved in epigenetic regulation (Shih et al. 2012).

Related Pathways

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D., Stephen W. Clark, M.D., Ph.D., Annette S. Kim, M.D., Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones, S. Clark, A. Kim. 2015. IDH2. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/idh2/?tab=0 (Updated December 4).

Last Updated: December 4, 2015

IDH2 in Acute Myeloid Leukemia

IDH2 is mutated in 9.1% of acute myeloid leukemia cases (COSMIC). Mutations of the R140 or R172 residues both result in a protein with different function; the new function is believed to contribute to leukemogenesis by inhibiting normal epigenetic regulation (Feng et al. 2012; Green et al. 2011; Jeziskova et al. 2010; Shih et al. 2012; Zhou et al. 2012). IDH2 mutations fall outside the “two-hit” theory of leukemogenesis as it was originally conceived. Some have proposed categorizing IDH2 mutations into a new class of mutations; members of the new class—class III—would be defined as mutations occurring in epigenetic modifiers (Naoe and Kiyoi 2013; Shih et al. 2012). Similar to DNMT3A and IDH1 mutations, IDH2 mutations affect DNA methylation and as such, play a role in cancer development through deregulation of gene expression.​​​

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones. 2013. IDH2 in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/idh2/ (Updated October 1).

Last Updated: October 1, 2013

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