Mutant IDH: a targetable driver of leukemic phenotypes linking metabolism, epigenetics and transcriptional regulation. Review uri icon

Overview

abstract

  • Aberrant epigenomic programming is a hallmark of acute myeloid leukemia. This is partially due to somatic mutations that perturb cytosine methylation, histone post-translational modifications and transcription factors. Remarkably, mutations in the IDH1 and IDH2 genes perturb the epigenome through all three of these mechanisms. Mutant IDH enzymes produce high levels of the oncometabolite (R)-2-hydroxyglutarate that competitively inhibits dioxygenase enzymes that modify methylcytosine to hydroxymethylcytosine and histone tail methylation. The development of IDH mutant specific inhibitors may now enable the therapeutic reprogramming of both layers of the epigenome spontaneously to revert the malignant phenotype of these leukemias and improve clinical outcome for acute myeloid leukemia patients with IDH mutations.

publication date

  • July 19, 2016

Research

keywords

  • Isocitrate Dehydrogenase

Identity

PubMed Central ID

  • PMC5066133

Scopus Document Identifier

  • 84980329545

Digital Object Identifier (DOI)

  • 10.2217/epi-2016-0008

PubMed ID

  • 27431380

Additional Document Info

volume

  • 8

issue

  • 7