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Metabolite common among cancers

09.02.2010
A study published online on February 8 in the Journal of Experimental Medicine (www.jem.org) reports that several distinct mutations found in a subset of patients with acute myelogenous leukemia (AML) result in excess production of the same metabolite.

The enzyme isocitrate dehydrogenase 1 (IDH1), which normally facilitates production of the metabolite {alpha}-ketoglutarate, is mutated in approximately 80% of secondary brain tumors. This mutant version of IDH1 promotes excess production of a different metabolite: R (-)-2-hydroxyglutarate (2-HG).

A team led by Tak Mak (Toronto) detected elevated concentrations of 2-HG in the serum of the approximately 8% of AML patients with mutations in IDH1. In addition, they identified a mutation in IDH2—the sister enzyme of IDH1—in some AML patients. These patients also had unusually high serum levels of 2-HG.

Additional work is needed to understand if and how 2-HG influences brain cancer and/or leukemia progression. However, as these mutations have so far only been found in cancer, they may prove useful as drug targets.

About The Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JEM content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license.

Gross, S., et al. 2010. J. Exp. Med. doi:10.1084/jem.20092506

Rita Sullivan | EurekAlert!
Further information:
http://www.rupress.org
http://www.jem.org

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