Dataset Information

Molecular Pathways: IDH2 Mutations-Co-opting Cellular Metabolism for Malignant Transformation.

ABSTRACT: Mutations in mitochondrial IDH2, one of the three isoforms of IDH, were discovered in patients with gliomas in 2009 and subsequently described in acute myelogenous leukemia (AML), angioimmunoblastic T-cell lymphoma, chondrosarcoma, and intrahepatic chloangiocarcinoma. The effects of mutations in IDH2 on cellular metabolism, the epigenetic state of mutated cells, and cellular differentiation have been elucidated in vitro and in vivo. Mutations in IDH2 lead to an enzymatic gain of function that catalyzes the conversion of alpha-ketoglutarate to beta-hydroxyglutarate (2-HG). Supranormal levels of 2-HG lead to hypermethylation of epigenetic targets and a subsequent block in cellular differentiation. AG-221, a small-molecule inhibitor of mutant IDH2, is being explored in a phase I clinical trial for the treatment of AML, other myeloid malignancies, solid tumors, and gliomas.

SUBMITTER: Stein EM

PROVIDER: S-EPMC5050039 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Molecular Pathways: IDH2 Mutations-Co-opting Cellular Metabolism for Malignant Transformation.

Stein Eytan M EM

Clinical cancer research : an official journal of the American Association for Cancer Research 20151109 1

Mutations in mitochondrial IDH2, one of the three isoforms of IDH, were discovered in patients with gliomas in 2009 and subsequently described in acute myelogenous leukemia (AML), angioimmunoblastic T-cell lymphoma, chondrosarcoma, and intrahepatic chloangiocarcinoma. The effects of mutations in IDH2 on cellular metabolism, the epigenetic state of mutated cells, and cellular differentiation have been elucidated in vitro and in vivo. Mutations in IDH2 lead to an enzymatic gain of function that ca ...[more]

PMID: 26553750

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Dataset Information

Molecular Pathways: IDH2 Mutations-Co-opting Cellular Metabolism for Malignant Transformation.

Publications

Molecular Pathways: IDH2 Mutations-Co-opting Cellular Metabolism for Malignant Transformation.

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