The DOI matches its Crossref record; 93 of the 95 references it cites were found in a registry or an index.
Clonal Hematopoiesis: Mechanisms Driving Dominance of Stem Cell Clones
Open accessAbstract
The discovery of clonal hematopoiesis (CH) in older individuals has changed the way hematologists and stem cell biologists view aging. Somatic mutations accumulate in stem cells over time. While most mutations have no impact, some result in subtle functional differences that ultimately manifest in distinct stem cell behaviors. With a large pool of stem cells and many decades to compete, some of these differences confer advantages under specific contexts. About 20 genes are recurrently found as mutated in CH, indicating they confer some advantage. The impact of these mutations has begun to be analyzed at a molecular level by modeling in cell lines and in mice. Mutations in epigenetic regulators such as DNMT3A and TET2 confer an advantage by enhancing self-renewal of stem and progenitor cells and inhibiting their differentiation. Mutations in other genes involved in the DNA damage response may simply enhance cell survival. Here, we review proposed mechanisms that lead to CH, specifically in the context of stem cell biology, based on our current understanding of the function of some of the CH-associated genes.
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“Most DNMT3A variants in human CH are missense heterozygous loss-of-function (6).”
From Txnip Enhances Fitness of Dnmt3a -Mutant Hematopoietic Stem Cells via p21 (2022) · cites this paper as [6]
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“Approximately 50% of all genetic variants in CH occur in the gene DNMT3A (6), which encodes a de novo DNA methyltransferase enzyme responsible for establishing new DNA methylation patterns during development and stem cell fate decisions (7,8).”
From Txnip Enhances Fitness of Dnmt3a -Mutant Hematopoietic Stem Cells via p21 (2022) · cites this paper as [6]
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Citations
Cites
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Cited by
Sorted by citations
Ageing and rejuvenation of tissue stem cells and their niches
Brunet, A., Goodell, M. A., & Rando, T. A. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00510-w · Cited by 407
Self-citationdos Santos, D. M. C., Tix, T., Shouval, R., Gafter-Gvili, A., Alberge, J.-B., Cliff, E. R. S., Theurich, S., von Bergwelt-Baildon, M., Ghobrial, I., Subklewe, M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03084-6 · Cited by 266
Leukemic stem cells and therapy resistance in acute myeloid leukemia
Stelmach, P., & Trumpp, A. (2023) · Haematologica · doi:10.3324/haematol.2022.280800 · Cited by 273
Somatic Mutations in “Benign” Disease
Mustjoki, S. M., & Young, N. S. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2101920 · Cited by 169
Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects
Robertson, N. A., Latorre-Crespo, E., Terradas-Terradas, M., Lemos-Portela, J., Purcell, A. C., Livesey, B. J., Hillary, R. F., Murphy, L., Fawkes, A., MacGillivray, L., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01883-3 · Cited by 132
Metadata
- Authors
- Challen, G., & Goodell, M. A.
- Affiliations
- Washington University in St. Louis (US)
- Baylor College of Medicine (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-08-03
- Volume
- 136
- Issue
- 14
- Pages
- 1590-1598
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC7530644
- OpenAlex
- W3047537073
- Cited by
- 131
- References
- 95
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 20 · 2023: 30 · 2022: 37 · 2021: 22 · 2020: 1
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Keywords
- clonal hematopoiesis, hematopoietic stem cells, somatic mutations, aging, DNMT3A, TET2, epigenetic regulators, DNA damage response, stem cell self-renewal, stem cell differentiation, clonal dominance, recurrent mutations
- MeSH terms
- Discoidin Domain Receptors, Clonal Hematopoiesis, DNA Methyltransferase 3A, Animals, Cell Differentiation, DNA (Cytosine-5-)-Methyltransferases, DNA Damage, DNA-Binding Proteins, Hematopoiesis, Humans, Mutation, Proto-Oncogene Proteins, Stem Cells, Biomarkers, Gene Expression Regulation, Developmental, Dioxygenases, Clonal Evolution
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