The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency
Our study indicates that inhibiting KAT6A KAT activity holds compelling promise for KAT6Ar AML patients. In contrast, targeted degradation of KAT6A, and not just its catalytic activity, may represent a more appropriate therapeutic approach for KMT2Ar AMLs.
Authors
- Liam Clayfield (ORCID: https://orcid.org/0000-0001-7750-5080)
- Natalia Moncaut
- Georges Lacaud (ORCID: https://orcid.org/0000-0002-5630-2417)
- Mathew Sheridan (ORCID: https://orcid.org/0000-0003-0628-7674)
- Jérôme Paggetti (ORCID: https://orcid.org/0000-0001-9460-5876)
- Syed Murtuza Baker (ORCID: https://orcid.org/0000-0002-6633-333X)
- Valérie Kouskoff (ORCID: https://orcid.org/0000-0001-9801-4993)
- Romain Aucagne (ORCID: https://orcid.org/0000-0002-5644-3287)
- Jessica S. Whittle (ORCID: https://orcid.org/0000-0003-3177-8934)
- Robert M. Sellers (ORCID: https://orcid.org/0000-0002-8193-9356)
- Laurent Delva (ORCID: https://orcid.org/0000-0002-1086-3964)
- Anne Largeot (ORCID: https://orcid.org/0000-0002-9388-8461)
- Michael Lie‐A‐Ling (ORCID: https://orcid.org/0000-0003-0194-4313)
- Muhammad Ahmad Maqbool (ORCID: https://orcid.org/0000-0001-6757-0866)
- Mudassar Iqbal (ORCID: https://orcid.org/0000-0002-5006-4331)
- Jingru Xu (ORCID: https://orcid.org/0000-0001-5189-3986)
Institutions
- Inserm (FR)
- Université de Bourgogne (FR)
- Age UK (GB)
- University of Manchester (GB)
- Luxembourg Institute of Health (LU)
- Cancer Research UK Manchester Institute (GB)
Publication Details
- Journal
- Journal of Hematology & Oncology
- Published
- 2024-10-08
- DOI
- https://doi.org/10.1186/s13045-024-01610-0
- Citations
- 8
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 3.64
Funders
- Cancer Research UK
- Fonds National de la Recherche Luxembourg
- Blood Cancer UK
- Cancer Research UK Manchester Centre
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Erasmus Universitair Medisch Centrum Rotterdam
- HORIZON EUROPE Marie Sklodowska-Curie Actions