Dual Proteasome and Histone Deacetylase Inhibition Overcomes Tyrosine Kinase Inhibitor Resistance in Breakpoint Cluster Region: Abelson 1-Driven Leukaemia Cell Lines.

ABSTRACT: Resistance to tyrosine kinase inhibitors (TKIs) remains a major challenge in breakpoint cluster region (BCR)::Abelson 1 (ABL1)-driven leukaemias. Asciminib offers a novel therapeutic option; however, resistance continues to emerge. We hypothesised that targeting proteostasis and epigenetic regulation with bortezomib and panobinostat could eliminate TKI-refractory cells via TKI-independent mechanisms. We profiled parental and TKI-resistant chronic myelogenous leukaemia (CML) and Ba/F3 models. Viability, cytotoxicity, and caspase-3/7 activity were assessed following single-agent treatment with asciminib, ponatinib, bortezomib, or panobinostat. The effects of the bortezomib-panobinostat combination on colony formation, mitochondrial membrane potential, and apoptosis were evaluated. Asciminib

SUBMITTER: Okabe S 

PROVIDER: S-EPMC12908417 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature