Document Type
Article
Publication Date
5-15-2026
Abstract
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.
Recommended Citation
Goetz, Melanie L.; Romer-Seibert, Jennifer S.; Versace, Amanda M.; Kogan, Scott; Jeurkar, Chetan; Bowman, Robert L.; Brooks, Nigel; Frese, Kris; and Meyer, Sara E., "P300/CBP Inhibition with Inobrodib in Combination with Gilteritinib and Venetoclax Targets Leukemia Stem Cells in Epigenetic Mutant AML" (2026). Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers. Paper 64.
https://jdc.jefferson.edu/ppcbfp/64
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
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Language
English
Included in
Cancer Biology Commons, Pharmacology Commons, Physiology Commons
Comments
This article is the author's final published version in Science Advances, Volume 12, Issue 20, 2026, Article number eaec9305.
The published version is available at https://doi.org/10.1126/sciadv.aec9305. Copyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.