Clonal Hematopoiesis
Definition
Clonal hematopoiesis refers to the expansion of a blood-forming stem or progenitor cell and its descendants so that one genetically distinct clone contributes a measurable share of blood production. In ageing research, the term often refers to age-associated clones carrying somatic mutations in genes such as DNMT3A, TET2, or ASXL1. [1] [2] [3]
A related term, clonal hematopoiesis of indeterminate potential (CHIP), is used when such a clone is detected in blood or marrow without diagnostic evidence of a hematologic malignancy or another defined clonal blood disorder. [2] [4]
Why It Matters in Ageing Research
Clonal hematopoiesis becomes more common with age, which makes it relevant to the biology of ageing rather than only to cancer biology. Large sequencing studies showed that detectable clonal hematopoiesis is uncommon in younger adults but much more frequent in older populations, with prevalence estimates rising into later life depending on sequencing depth and clone-size thresholds. [1] [3] [5]
It also matters because these clones are associated with increased risk of hematologic malignancy and have been linked to nonmalignant age-related conditions, especially atherosclerotic cardiovascular disease and inflammatory phenotypes. This has shifted clonal hematopoiesis from being viewed only as a premalignant signal to being studied as one way ageing blood systems may influence broader late-life disease risk. [1] [4] [6]
Common Confusion
- Clonal hematopoiesis is not itself a diagnosis of leukemia or myelodysplastic syndrome. [2] [4]
- Not every detectable clone has the same implications; risk depends on factors such as the mutated gene, clone size, and clinical context. [4] [6]
- CHIP is a narrower category than clonal hematopoiesis overall, because it specifically excludes overt hematologic disease and other defined clonal disorders. [2] [4]
Related Reading
References
- Genovese, G., et al. (2014). Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence. https://pmc.ncbi.nlm.nih.gov/articles/PMC4290021/
- Steensma, D. P., et al. (2015). Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. https://pmc.ncbi.nlm.nih.gov/articles/PMC4624443/
- Jan, M., Ebert, B. L., and Jaiswal, S. (2017). Clonal hematopoiesis. https://pmc.ncbi.nlm.nih.gov/articles/PMC8045769/
- Shlush, L. I. (2018). Age-related clonal hematopoiesis. https://pubmed.ncbi.nlm.nih.gov/29141946/
- Acuna-Hidalgo, R., et al. (2017). Ultra-sensitive Sequencing Identifies High Prevalence of Clonal Hematopoiesis-Associated Mutations throughout Adult Life. https://pmc.ncbi.nlm.nih.gov/articles/PMC5501773/
- Jaiswal, S. (2020). Clonal hematopoiesis and nonhematologic disorders. https://pmc.ncbi.nlm.nih.gov/articles/PMC8209629/
This glossary entry is provided for educational purposes only and does not constitute medical advice.