The Common Feature of Leukemia-associated IDH1 and IDH2 Mutations is a Neomorphic Enzyme Activity Converting Alpha-ketoglutarate to 2-hydroxyglutarate

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2010 Feb 23

PMID 20171147

Citations 1012

Authors

Patrick S Ward

Jay Patel

David R Wise

Omar Abdel-Wahab

Bryson D Bennett

Hilary A Coller

Justin R Cross

Valeria R Fantin

Cyrus V Hedvat

Alexander E Perl

Joshua D Rabinowitz

Martin Carroll

Shinsan M Su

Kim A Sharp

Ross L Levine

Craig B Thompson

Affiliations

Soon will be listed here.

Abstract

The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). Here, we report that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Surprisingly, less than half of cases with elevated 2HG possessed IDH1 mutations. The remaining cases with elevated 2HG had mutations in IDH2, the mitochondrial homolog of IDH1. These data demonstrate that a shared feature of all cancer-associated IDH mutations is production of the oncometabolite 2HG. Furthermore, AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis.

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