Mechanisms of chemotherapy failure in refractory/relapsed acute myeloid leukemia: the role of cytarabine resistance and mitochondrial metabolism.

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Patients with wild-type FLT3 relapsed or refractory (R/R) AML face significant therapeutic challenges due to the persistent lack of effective treatments. A comprehensive understanding of the mechanisms underlying chemotherapy resistance is needed to the development of effective treatment strategies. Therefore, we investigated the molecular mechanisms underlying cytarabine (Ara-C) resistance and daunorubicin (DNR) tolerance in Ara-C-resistant RHI-1 cells derived from the wild-type FLT3 AML cell line SHI-1. Quantitative analysis of intracellular drug concentrations, proteomics, and phosphoproteomics showed that DNR resistance in Ara-C-resistant RHI-1 cells is driven by metabolic remodeling toward mitochondrial metabolism

SUBMITTER: Yeon Chae S 

PROVIDER: S-EPMC12019594 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature