Overall, this focussed drug screen demonstrates that CREBBP-mutated B-ALL is: (i) not uniformly chemo-resistant, and (ii) identifies a number of clinically-actionable agents for use in CREBBP-mutated high-risk B-ALL, including Dexamethasone, EP300 inhibitors and a potent sensitization to the BCL2 inhibitor Venetoclax. The gene discussed is CREBBP; the disease is acute lymphoblastic leukemia.