GSK-J4 treatment also induced Bcl-2 and Bcl-XL dependency and apoptosis.<h4>Conclusions</h4>This study proposes H3K27 demethylase inhibition as a potential treatment strategy for patients with treatment-resistant ALL, using CREBBP as a biomarker for drug response and combining GSK-J4 with venetoclax and navitoclax as synergistic partners. Here, CREBBP is linked to acute lymphoblastic leukemia.