Human <i>TET2</i> -Mutant Clonal Hematopoiesis Expansion Is Driven by Distinct Inflammatory Signaling Responses in Stem Cells Versus Myeloid Progeny
This study reveals that stress conditions inducing emergency myelopoiesis expand human TET2-mutant clones. TET2 mutation triggers an epigenetic silencing of AP-1 factors contributing to the dampening of the inflammatory responsiveness in TET2mut HSPCs while simultaneously promoting hyperinflammatory TET2mut monocyte-macrophage activation and differentiation, reinforcing inflammation.
Authors
- Miriam Llorian (ORCID: https://orcid.org/0000-0003-2582-6602)
- Eric D. Jong (ORCID: https://orcid.org/0000-0003-1117-9555)
- Katherine Sturgess (ORCID: https://orcid.org/0000-0002-6969-4747)
- Fatihah Mohamad Nor (ORCID: https://orcid.org/0009-0003-6787-0713)
- Dominique A. Bonnet (ORCID: https://orcid.org/0000-0002-4735-5226)
- Hector Huerga Encabo (ORCID: https://orcid.org/0000-0002-3723-8624)
- Giuseppe D’Agostino (ORCID: https://orcid.org/0000-0001-8315-7406)
- Syed A. Mian (ORCID: https://orcid.org/0000-0001-8005-2860)
- Gabriella Ficz (ORCID: https://orcid.org/0000-0001-9313-9578)
- Karl Habel (ORCID: https://orcid.org/0009-0007-6471-1468)
- L. Michael Graver (ORCID: https://orcid.org/0000-0002-1267-5916)
- Steven Ngo (ORCID: https://orcid.org/0000-0003-0132-873X)
- Despoina Papazoglou (ORCID: https://orcid.org/0009-0008-5818-8663)
- Fernando Anjos‐Afonso (ORCID: https://orcid.org/0000-0003-4392-488X)
- Linda Ariza-McNaughton (ORCID: https://orcid.org/0000-0002-8900-0984)
- Manuel Garcia‐Albornoz (ORCID: https://orcid.org/0000-0002-2300-2047)
- Aneesh Sharma (ORCID: https://orcid.org/0000-0002-8025-6772)
- Alessandra Ferrelli (ORCID: https://orcid.org/0000-0003-2308-1352)
- Alice E. Lord (ORCID: https://orcid.org/0000-0003-4238-4754)
- A. Ramesh (ORCID: https://orcid.org/0000-0003-4936-7754)
- Helene Foissner (ORCID: https://orcid.org/0009-0000-0378-4961)
Institutions
- Queen Mary University of London (GB)
- The Francis Crick Institute (GB)
- Plasticell (United Kingdom) (GB)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0070
- Citations
- 1
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.77