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Investigates a triplet combination therapy aiming to target leukemia stem cells in AML, suggesting a new therapeutic strategy.
Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3 -mutant AML by impairing pro-oncogenic survival and proliferation factors to effectively block leukemogenesis. This work identifies potential clinical utility of a targeted, triplet combination therapy for treatment of AML.
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Goetz et al. (2026) studied this question.
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