Catalytic Inhibition of KAT6/KAT7 Enhances the Efficacy and Overcomes Primary and Acquired Resistance to Menin Inhibitors in MLL Leukemia
This study provides the molecular rationale for combined targeting of KAT6/7 and menin in MLL leukemia. It reveals that combination therapy results in a rapid and profound repression of the MLL transcriptional program leading to marked differentiation and loss of leukemia-initiating capacity, setting the platform for clinical translation.
Authors
- Katie Fennell (ORCID: https://orcid.org/0000-0002-9476-5914)
- Laura MacPherson (ORCID: https://orcid.org/0000-0003-3422-4478)
- Kathy Knezevic (ORCID: https://orcid.org/0000-0002-3940-3363)
- Yih-Chih Chan (ORCID: https://orcid.org/0000-0003-2177-5406)
- Jakub Horvath
- Scott A. Armstrong (ORCID: https://orcid.org/0000-0002-9099-4728)
- Shellaina J.V. Gordon (ORCID: https://orcid.org/0000-0002-1675-3766)
- Daniela V. Wenge (ORCID: https://orcid.org/0000-0002-0064-9104)
- Brendon J. Monahan (ORCID: https://orcid.org/0000-0002-9545-8246)
- Dane Vassiliadis (ORCID: https://orcid.org/0000-0002-7814-4851)
- Michelle A. Camerino (ORCID: https://orcid.org/0000-0002-3352-3882)
- Wallace Bourgeois (ORCID: https://orcid.org/0000-0002-6935-8890)
- John D. Lapek (ORCID: https://orcid.org/0000-0002-6578-5350)
- Ian P. Street (ORCID: https://orcid.org/0000-0003-2684-4239)
- Xinmeng Jasmine Mu (ORCID: https://orcid.org/0000-0002-8079-0828)
- Enid Y.N. Lam (ORCID: https://orcid.org/0000-0001-5843-7836)
- Shikhar Sharma
- Jesse J. Balic (ORCID: https://orcid.org/0000-0002-9681-6834)
- Thomas A. Paul (ORCID: https://orcid.org/0000-0002-6465-886X)
- Mark A. Dawson (ORCID: https://orcid.org/0000-0002-5464-5029)
- Henrietta Holze (ORCID: https://orcid.org/0000-0003-1589-3887)
- Ylva E. Bozikis (ORCID: https://orcid.org/0009-0008-2245-2186)
- Paul A. Stupple (ORCID: https://orcid.org/0000-0002-3188-596X)
- Andrea Gillespie (ORCID: https://orcid.org/0000-0002-0447-7127)
- Florian Perner (ORCID: https://orcid.org/0000-0003-1010-3321)
- Sean Uryu
- Elanor N. Wainwright (ORCID: https://orcid.org/0000-0001-6409-3881)
- Benjamin J. Blyth (ORCID: https://orcid.org/0000-0003-4754-6249)
- Ahmet Murat
- Joan Cao
- Jeffrey R. White
- Thomas Plenge
- Tabea Klaus (ORCID: https://orcid.org/0009-0004-1629-5664)
- Jelena Petrovic
Institutions
- The University of Melbourne (AU)
- Pfizer (United States) (US)
- Peter MacCallum Cancer Centre (AU)
- UNSW Sydney (AU)
- Medizinische Hochschule Hannover (DE)
- Children's Cancer Institute Australia (AU)
- Dana-Farber Cancer Institute (US)
- Kratos Defense & Security Solutions (United States) (US)
- Dana-Farber Brigham Cancer Center (US)
- Monash University (AU)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-06-19
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-1517
- Citations
- 12
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 21.24