Molecular insights into chemotherapy resistance mediated by MLL-AF9 fusion gene in pediatric B-cell acute lymphoblastic leukemia.

ABSTRACT: This research utilized multiomics data to elucidate the molecular mechanisms of chemotherapy resistance in pediatric B-cell acute lymphoblastic leukemia driven by the MLL-AF9 fusion gene. Transcriptome data from B-ALL patients in the Gene Expression Omnibus and Therapeutically Applicable Research to Generate Effective Treatments databases were analyzed using weighted gene coexpression network analysis, identifying IGFBP7 as a critical gene associated with MLL-AF9 rearrangement. The MLL-AF9 fusion upregulated IGFBP7, activating ABCB1 transporters and the DNA-PKcs-mediated non-homologous end joining (NHEJ) repair pathway, thereby promoting chemoresistance. In vitro experiments demonstrated that MLL-AF9-overexpressing B-ALL cells exhibited reduced sensitivity to doxorubicin (DOX), cyclophosph

SUBMITTER: Sang X 

PROVIDER: S-EPMC12269502 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature