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Review
. 2021 Jun 3;11(6):107.
doi: 10.1038/s41408-021-00497-1.

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

Ghayas C Issa  1 , Courtney D DiNardo  2
Affiliations
Review

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

Ghayas C Issa et al. Blood Cancer J. .

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.

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Conflict of interest statement

G.C.I. received research funding from Celgene, Kura Oncology, Syndax and Novartis, and received consultancy fees from Novartis and Kura Oncology. C.D.D. received research funding from AbbVie, Agios, Novartis, Celgene, Daiichi-Sankyo, Calithera Biosciences, Jazz Pharmaceuticals, Notable Laboratories, and received consultancy fees from AbbVie, Agios, Novartis, Celgene, Daiichi-Sankyo, and Jazz Pharmaceuticals.

Figures

Fig. 1
Fig. 1. A timeline depicting the decade of progress in IDH-mutated malignancies.
IDH, Isocitrate Dehydrogenase; 2HG, 2-hydroxyglutarate; AML, acute myeloid leukemia; TET2, Ten-Eleven Translocation-2; 2-OG, 2-oxygluterate; AITL, angioimmunoblastic T-cell lymphoma.
Fig. 2
Fig. 2. Treatment algorithm for AML with mutated IDH1 or IDH2.
AML, acute myeloid leukemia; IDH, Isocitrate Dehydrogenase; HMA, hypomethylating agent; IDHi, IDH inhibitor; Allo-HSCT, allogeneic hematopoietic stem cell transplant; MRD, minimal or measurable residual disease.
See this image and copyright information in PMC

References

    1. Mardis ER, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 2009;361:1058–1066. doi: 10.1056/NEJMoa0903840. - DOI - PMC - PubMed
    1. DiNardo CD, et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am. J. Hematol. 2015;90:732–736. doi: 10.1002/ajh.24072. - DOI - PMC - PubMed
    1. Molenaar RJ, et al. Clinical and biological implications of ancestral and non-ancestral IDH1 and IDH2 mutations in myeloid neoplasms. Leukemia. 2015;29:2134–2142. doi: 10.1038/leu.2015.91. - DOI - PMC - PubMed
    1. Ward PS, et al. The potential for isocitrate dehydrogenase mutations to produce 2-hydroxyglutarate depends on allele specificity and subcellular compartmentalization. J. Biol. Chem. 2013;288:3804–3815. doi: 10.1074/jbc.M112.435495. - DOI - PMC - PubMed
    1. Dang L, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739–744. doi: 10.1038/nature08617. - DOI - PMC - PubMed

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