SUMOylation inhibition potentiates the glucocorticoid receptor to program growth arrest of acute lymphoblastic leukemia cells.

ABSTRACT: Glucocorticoids are a mainstay in the treatment of B-cell acute lymphoblastic leukemia (B-ALL). The glucocorticoid receptor (GR), a ligand-activated transcription factor (TF), mediates their actions. Chromatin occupancy, chromatin-protein networks (chromatomes) and gene programmes of GR are regulated by SUMOylation, a post-translational modification with therapeutic implications in other hematomalignancies. To unravel the GR-SUMOylation crosstalk in B-ALL, we induced hypoSUMOylation in NALM6 B-ALL cells with a SUMOylation inhibitor (SUMOi, ML-792). Genome-wide profiling of GR and SUMO chromatin-binding and chromatin accessibility revealed that hypoSUMOylation augmented GR chromatin occupancy and altered chromatin openness. Association with transcriptome data indicated that the hypoSUMOylat

SUBMITTER: Valima E 

PROVIDER: S-EPMC12048349 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature