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Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm.

ABSTRACT: Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2. These recurrent mutations in key metabolic enzymes lead to the production of the oncometabolite 2-hydroxyglutarate, which promotes leukemogenesis through a block in normal myeloid differentiation. Since this discovery, selective oral inhibitors of mutant IDH1 and IDH2 have subsequently been developed and are now approved as single agent therapy, based on clinical efficacy observed within the original first-in-human trials. The investigation of IDH inhibitors in combination with standard therapies such as azacytidine, with intensive chemotherapy, and with other small molecule targeted therapies in rational combinations are currently under evaluation to further improve upon clinical efficacy.

SUBMITTER: Issa GC

PROVIDER: S-EPMC8175383 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm.

Issa Ghayas C GC DiNardo Courtney D CD

Blood cancer journal 20210603 6

Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2. These recurrent mutations in key metabolic enzymes lead to the production of the oncometabolite 2-hydroxyglutarate, which promotes leukemogenesis through a block in normal myeloid differentiation. Since this discovery, selective oral inhibitors of mutant IDH1 and IDH2 have subsequently been developed and are now appro ...[more]

PMID: 34083508

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