Increasing H3K9 Methylation Level Reduces the Proliferation of Leukemic Stem Cells
Background/Objectives: Genetic and epigenetic alterations accumulate throughout life in hematopoietic stem and progenitor cells (HSPCs), leading to an increased risk of age-related hematological malignancies, such as acute myeloid leukemia (AML). While a few epigenetic drugs have entered clinical practice, studies focusing on histone post-translational modifications (PTMs) altered in AML remain limited. Methods: Here, we used murine HSPCs, murine AML mouse models, human leukemic cell lines, and leukemic patient samples to investigate whether targeting the methylation of histone 3 at lysine 9 (H3K9 methylation) affects HSPCs upon aging and leukemogenesis and might represent a possible target. Results: Our data show that H3K9 methylation changes upon aging in HSPCs and is linked to a pre-malignant phenotype. Low levels of H3K9 methylation in leukemic cells are required to maintain proliferative capacities in vitro. Increasing H3K9 methylation reduces the leukemogenesis of both young and aged murine and patient-derived leukemic cells. Conclusions: Thus, H3K9 methylation might be a potential and selective therapeutic target in AML patients.
Authors
- Javier Lozano-Bartolomé (ORCID: https://orcid.org/0000-0003-2518-1381)
- Polina Zjablovskaja
- Liam MacPhee
- Meritxell Alberich-Jordà (ORCID: https://orcid.org/0000-0002-8093-641X)
- Michael Lübbert (ORCID: https://orcid.org/0000-0003-1186-1650)
- Amanda Amoah (ORCID: https://orcid.org/0000-0002-1267-4091)
- Maria Carolina Florian (ORCID: https://orcid.org/0000-0002-5791-1310)
- Sara Montserrat‐Vazquez (ORCID: https://orcid.org/0000-0001-8516-7077)
- Miroslava K. Adamcová (ORCID: https://orcid.org/0000-0001-5025-8155)
- Qin Peng (ORCID: https://orcid.org/0000-0001-8364-3885)
- A. MAUREEN ROUHI (ORCID: https://orcid.org/0000-0002-6450-027X)
- Chang Sun (ORCID: https://orcid.org/0000-0002-3988-5462)
- Eva Mejía-Ramírez (ORCID: https://orcid.org/0000-0003-1251-5223)
- Melika Bakharzi
- Barbara Walter (ORCID: https://orcid.org/0000-0002-0844-5958)
- Montserrat Arnan-Sangerman
- Jasson Villarreal (ORCID: https://orcid.org/0009-0009-4865-2749)
- Laia Solé-Castilla (ORCID: https://orcid.org/0009-0002-0646-8272)
- Florian Kuchenbauer
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of British Columbia (CA)
- Universität Ulm (DE)
- Czech Academy of Sciences (CZ)
- University Medical Center Freiburg (DE)
- Vancouver General Hospital (CA)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Terry Fox Research Institute (CA)
- Shenzhen Bay Laboratory (CN)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Institut Català d'Oncologia (ES)
- Institute of Molecular Genetics (RU)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- Center of Regenerative Medicine in Barcelona (ES)
- Technische Hochschule Ulm (DE)
Publication Details
- Journal
- Cancers
- Published
- 2026-09-14
- DOI
- https://doi.org/10.3390/cancers18182969
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00