Ramsey HE, Greenwood D, Zhang S, Childress M, Arrate MP, Gorska AE, Fuller L, Zhao Y, Stengel K, Fischer MA, Stubbs MC, Liu PCC, Boyd K, Rathmell JC, Hiebert SW, Savona MR. BET Inhibition Enhances the Antileukemic Activity of Low-dose Venetoclax in Acute Myeloid Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Dec 15;27(27). 598-607. PMID: 33148670 [PubMed]
The BCL2 inhibitor, venetoclax, has transformed clinical care in acute myeloid leukemia (AML). However, subsets of patients do not respond or eventually acquire resistance. Venetoclax-based regimens can lead to considerable marrow suppression in some patients. Bromodomain and extraterminal inhibitors (BETi) are potential treatments for AML, as regulators of critical AML oncogenes. We tested the efficacy of novel BET inhibitor INCB054329, and its synergy with venetoclax to reduce AML without induction of hematopoietic toxicity.