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Comment
. 2013 Mar 18;23(3):274-6.
doi: 10.1016/j.ccr.2013.03.005.

R-2-hydroxyglutarate as the key effector of IDH mutations promoting oncogenesis

Dan Ye  1 , Shenghong Ma, Yue Xiong, Kun-Liang Guan
Affiliations
Comment

R-2-hydroxyglutarate as the key effector of IDH mutations promoting oncogenesis

Dan Ye et al. Cancer Cell. .

Abstract

The tumor-associated isocitrate dehydrogenase (IDH) mutants are unique in that they have lost their normal catalytic activity and gained a novel function to produce R-2-hydroxyglutarate (R-2-HG). A recent study now shows that R-2-HG can reversibly promote leukemogenesis in vitro, suggesting a therapeutic potential of targeting mutant IDH1 and IDH2.

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Figures

Figure 1
Figure 1. A proposed model for R-2-HG in tumorigenesis
R-2-HG produced by the mutant IDH1/2 promotes tumorigenesis by inhibiting 5mC hydroxylase (TET2) and lysine demethylases (KDM) leading to demethylation of DNA and histone, respectively. The epigenetic alterations associated with IDH1/2 mutations result in changes of gene expression and tumorigenesis. These processes can be recapitulated by R-2-HG, demonstrating R-2-HG as a true oncometabolite. R-2-HG does not inhibit but rather stimulates EglN1, which promotes HIF1α degradation by hydroxylation. HIF1α might suppress leukemogenesis but this may not apply to other cancer types with IDH1/2 mutations.
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Comment on

References

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