Cited by 131Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationBlood disorders and treatments

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Clonal Hematopoiesis: Mechanisms Driving Dominance of Stem Cell Clones

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Challen, Grant, Goodell, Margaret A·2020·Blood

DOI 10.1182/blood.2020006510PMC PMC7530644

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Abstract

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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Authors: Challen, G., & Goodell, M. A.
Affiliations: Washington University in St. Louis (US)
Baylor College of Medicine (US)
ORCID: Challen, Grant
Goodell, Margaret A
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
DOI: 10.1182/blood.2020006510
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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Clonal Hematopoiesis: Mechanisms Driving Dominance of Stem Cell Clones

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