BCL3 expression promotes resistance to alkylating chemotherapy in gliomas

) promoter, high BCL-3 expression was associated with a poor response to TMZ. Mechanistically, BCL-3 promoted a more malignant phenotype by inducing an epithelial-to-mesenchymal transition in glioblastomas through promoter-specific NF-κB dimer exchange. Carbonic anhydrase II (CAII) was identified as a downstream factor promoting BCL-3-mediated resistance to chemotherapy. Experiments in glioma xenograft mouse models demonstrated that the CAII inhibitor acetazolamide enhanced survival of TMZ-treated animals. Our data suggest that BCL-3 might be a useful indicator of glioma response to alkylating chemotherapy and that acetazolamide might be repurposed as a chemosensitizer for treating TMZ-resistant gliomas.