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The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting @a-Ketoglutarate to 2-Hydroxyglutarate

Patrick S PS Ward, Jay J Patel, David R DR Wise, Omar O Abdel-Wahab, Bryson D BD Bennett, Hilary A HA Coller, Justin R JR Cross, Valeria R VR Fantin, Cyrus V CV Hedvat, Alexander E AE Perl, Joshua D JD Rabinowitz, Martin M Carroll, Shinsan M SM Su, Kim A KA Sharp, Ross L RL Levine, and Craig B CB Thompson

Cancer Cell 17(3):10 (2010) PMID 20171147 PMCID PMC2849316

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.

Copyright © 2010 Elsevier Ltd. All rights reserved.

Referenced by 1 articles

DOI: 10.1016/j.ccr.2010.01.020
Version: za2963e q8za1 q8zb9 q8zc8 q8zd2 q8zec q8zf5 q8zgf
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