Tandem Duplications in <i>UBTF</i> Create XPO1-Dependent Nuclear Export Signals that Reveal a Leukemic Therapeutic Dependency
UBTF tandem duplications are a high-risk AML subtype. We identified a mechanism in which UBTF-TDs result in the generation of NES motifs, enabling aberrant interaction with XPO1. We found that XPO1 inhibitors block this interaction and impair leukemia growth, identifying a possible therapeutic strategy in UBTF-TD AML. See related commentary by Adams, p. 15.
Authors
- Aaron H. Phillips (ORCID: https://orcid.org/0000-0003-0245-5124)
- Amit Kumar (ORCID: https://orcid.org/0000-0003-1720-8951)
- Jamila Moore (ORCID: https://orcid.org/0009-0005-6166-944X)
- Richard W. Kriwacki (ORCID: https://orcid.org/0000-0002-9798-6018)
- Ryan Hiltenbrand (ORCID: https://orcid.org/0000-0002-9267-9844)
- Jeffery M. Klco (ORCID: https://orcid.org/0000-0003-2961-6960)
- Tamara Westover (ORCID: https://orcid.org/0000-0002-1000-6698)
- Lisett Contreras (ORCID: https://orcid.org/0000-0002-7433-8413)
- Jing Ma (ORCID: https://orcid.org/0000-0003-2910-2628)
- Kelly Churion (ORCID: https://orcid.org/0000-0002-4346-7562)
- Chandra Rolle (ORCID: https://orcid.org/0009-0005-2763-9749)
- Evangelia K. Papachristou (ORCID: https://orcid.org/0000-0002-5835-2055)
- Lauren Ezzell (ORCID: https://orcid.org/0009-0009-1379-7104)
- Burgess B. Freeman (ORCID: https://orcid.org/0000-0003-2174-5119)
- Jina Wang (ORCID: https://orcid.org/0009-0001-3767-0214)
- Elizabeth Caldwell (ORCID: https://orcid.org/0009-0005-7992-8577)
- Guangchun Song (ORCID: https://orcid.org/0000-0001-9626-2598)
- Beisi Xu (ORCID: https://orcid.org/0000-0003-0099-858X)
- Melvin E. Thomas (ORCID: https://orcid.org/0000-0001-5813-1036)
- Emily Xiong (ORCID: https://orcid.org/0000-0002-0009-9210)
- Sandi Radko-Juettner (ORCID: https://orcid.org/0000-0002-6969-5184)
- Wenjie Qi (ORCID: https://orcid.org/0009-0006-0656-567X)
- Laura J. Janke (ORCID: https://orcid.org/0000-0002-9871-6239)
- Juan M. Barajas (ORCID: https://orcid.org/0000-0002-0664-5243)
- Clive S. D’Santos (ORCID: https://orcid.org/0000-0003-4592-0487)
- Michael P. Walsh (ORCID: https://orcid.org/0009-0000-4293-5291)
- Masayuki Umeda (ORCID: https://orcid.org/0009-0002-5636-6602)
- Josi Lott (ORCID: https://orcid.org/0009-0004-2504-8657)
Institutions
- St. Jude Children's Research Hospital (US)
- University of Tennessee Health Science Center (US)
- University of Cambridge (GB)
- Cancer Research UK Cambridge Center (GB)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2025-11-03
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0112
- Citations
- 1
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.77