IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors.

ABSTRACT: Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2^MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2^MUT AML is not known.Experimental Design: Well-characterized primary IDH1^MUT, IDH2^MUT, and IDH1/2^WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and PARP inhibitors.Results:IDH1/2^MUT caused increased DNA damage and sensitization to daunorubicin, ir

SUBMITTER: Molenaar RJ 

PROVIDER: S-EPMC5884732 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature