DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency
Understanding which driver mutations are required for cancer initiation, maintenance, or both phases remains poorly understood. In this study, we uncover that highly prevalent preleukemic DNMT3A mutations are only required during disease initiation but become dispensable after leukemic transformation, uncovering the context-specific role of this driver mutation with important therapeutic implications. See related commentary by Zhou and Huang, p. 428.
Authors
- Cailin Collins (ORCID: https://orcid.org/0000-0001-5025-0065)
- Kyle M. Loh (ORCID: https://orcid.org/0000-0002-8042-0149)
- Kensuke Kayamori (ORCID: https://orcid.org/0000-0001-6140-3135)
- Jonas L. Fowler (ORCID: https://orcid.org/0000-0003-0766-4320)
- Daiki Karigane (ORCID: https://orcid.org/0000-0002-4017-5193)
- Eleanor Hilgart (ORCID: https://orcid.org/0009-0003-9822-9160)
- Amy C. Fan (ORCID: https://orcid.org/0000-0003-1612-1862)
- Hiromitsu Nakauchi (ORCID: https://orcid.org/0000-0002-9841-6973)
- Yang Feng (ORCID: https://orcid.org/0000-0002-9533-1501)
- Fabian P. Suchy (ORCID: https://orcid.org/0000-0002-7187-5360)
- Michael A. Koldobskiy (ORCID: https://orcid.org/0000-0002-2980-6644)
- Thomas Köhnke (ORCID: https://orcid.org/0000-0001-7454-6282)
- Andrew P. Feinberg (ORCID: https://orcid.org/0000-0002-8364-1991)
- Ravindra Majeti (ORCID: https://orcid.org/0000-0002-5814-0984)
- Yusuke Nakauchi (ORCID: https://orcid.org/0000-0002-6943-3811)
- Athreya Rangavajhula (ORCID: https://orcid.org/0009-0002-1323-2671)
- Masashi Miyauchi (ORCID: https://orcid.org/0000-0002-6301-3429)
- Eduardo Martinez-Montes (ORCID: https://orcid.org/0000-0001-6241-1217)
Institutions
- Johns Hopkins University (US)
- Bunkyo University (JP)
- Palo Alto University (US)
- California Institute for Regenerative Medicine (US)
- Johns Hopkins Medicine (US)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- The University of Tokyo (JP)
- Stanford University (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-1604
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00