Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities.

Abstract excerpt

Heterozygous mutations in catalytic arginine residues of isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are common in glioma, acute myeloid leukemia, chondrosarcoma, cholangiocarcinoma, and angioimmunoblastic T-cell lymphoma. The mutant enzymes acquire a neomorphic activity that converts α-ketoglutarate (α-KG) to D-2-hydroxyglutarate (D2HG), a rare metabolite. In cells and tissues expressing mutant IDH, D2HG...

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