Epigenetic modification enhances the cytotoxicity of busulfan and4-hydroperoxycyclophosphamide in AML cells.

ABSTRACT: The combination of the DNA-alkylating agents busulfan (Bu) and cyclophosphamide is the most commonly used myeloablative pretransplantation conditioning therapy for myeloid leukemias. However, it is associated with significant nonrelapse mortality, which prohibits dose escalation to control relapse. We hypothesized that combining these two drugs with an epigenetic modifier would increase antileukemic efficacy without jeopardizing patient safety. A preclinical study was performed to determine the synergistic cytotoxicity of Bu, 4-hydroperoxycyclophosphamide (4HC), and the hypomethylating agent decitabine (DAC) in human acute myeloid leukemia (AML) cell lines. Exposure of KBM3/Bu250⁶ (P53-null) and OCI-AML3 (P53-wild-type) cells to Bu+4HC inhibited cell proliferation by ∼35-39%; ad

SUBMITTER: Valdez BC 

PROVIDER: S-EPMC6262883 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature