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Cited by 169Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationCancer Genomics and Diagnostics

Causes and consequences of clonal hematopoiesis

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Weeks, Lachelle D., Ebert, Benjamin L.·2023·Blood
DOI 10.1182/blood.2023022222PMC PMC10862247
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Abstract

Clonal hematopoiesis (CH) is described as the outsized contribution of expanded clones of hematopoietic stem and progenitor cells (HSPCs) to blood cell production. The prevalence of CH increases dramatically with age. CH can be caused by somatic mutations in individual genes or by gains and/or losses of larger chromosomal segments. CH is a premalignant state; the somatic mutations detected in CH are the initiating mutations for hematologic malignancies, and CH is a strong predictor of the development of blood cancers. Moreover, CH is associated with nonmalignant disorders and increased overall mortality. The somatic mutations that drive clonal expansion of HSPCs can alter the function of terminally differentiated blood cells, including the release of elevated levels of inflammatory cytokines. These cytokines may then contribute to a broad range of inflammatory disorders that increase in prevalence with age. Specific somatic mutations in the peripheral blood in coordination with blood count parameters can powerfully predict the development of hematologic malignancies and overall mortality in CH. In this review, we summarize the current understanding of CH nosology and origins. We provide an overview of available tools for risk stratification and discuss management strategies for patients with CH presenting to hematology clinics.

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  • The impact of somatic mutations on the aging brain is not fixed but is dynamically shaped by the specific driver gene, the local neuroinflammatory environment, and the integrity of the neurovascular unit.

    “These findings suggest that the impact of somatic mutations on the aging brain is not fixed but is instead dynamically shaped by the specific driver gene, the local neuroinflammatory environment, and the integrity of the neurovascular unit [42].”

    From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [42]

    Section 5.4 (Alzheimer’s Dementia; page unavailable) links CHIP to a reduced risk of Alzheimer’s dementia and suggests a possible role for altered activity of brain-resident microglial-like cells. Sections 3.1–3.2 and 7 describe genotype- and context-dependent effects of clonal hematopoiesis more broadly. The paper does not establish that its effects on the aging brain are shaped by the local neuroinflammatory environment or the integrity of the neurovascular unit. (LLM, conf=0.84)

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Authors
Weeks, L. D., & Ebert, B. L.
Affiliations
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Ebert, Benjamin L.
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2023-12-28
Volume
142
Issue
26
Pages
2235-2246
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.2023022222
PMC
PMC10862247
OpenAlex
W4388406603
Cited by
169
References
13
Citations by year
2026: 67 · 2025: 72 · 2024: 29 · 2023: 1
FWCI
8.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Blood (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Robert Wood Johnson Foundation
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Celgene
  • Dana-Farber Cancer Institute
  • Fondation Leducq
  • Swedish Orphan Biovitrum
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL082945)
  • National Cancer Institute (R35CA253125, P50CA206963, P01CA066996)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
clonal hematopoiesis, hematopoietic stem and progenitor cells, somatic mutations, chromosomal copy number alterations, hematologic malignancy risk, inflammatory cytokines, inflammatory diseases, mortality, risk stratification, clonal expansion, aging
MeSH terms
Clonal Hematopoiesis, Hematopoiesis, Humans, Mutation, Precancerous Conditions, Cytokines, Hematologic Neoplasms

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