Aging of the microenvironment influences clonality in hematopoiesis
Open accessAbstract
The mechanisms of the age-associated exponential increase in the incidence of leukemia are not known in detail. Leukemia as well as aging are initiated and regulated in multi-factorial fashion by cell-intrinsic and extrinsic factors. The role of aging of the microenvironment for leukemia initiation/progression has not been investigated in great detail so far. Clonality in hematopoiesis is tightly linked to the initiation of leukemia. Based on a retroviral-insertion mutagenesis approach to generate primitive hematopoietic cells with an intrinsic potential for clonal expansion, we determined clonality of transduced hematopoietic progenitor cells (HPCs) exposed to a young or aged microenvironment in vivo. While HPCs displayed primarily oligo-clonality within a young microenvironment, aged animals transplanted with identical pool of cells displayed reduced clonality within transduced HPCs. Our data show that an aged niche exerts a distinct selection pressure on dominant HPC-clones thus facilitating the transition to mono-clonality, which might be one underlying cause for the increased age-associated incidence of leukemia.
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As these HSCs clonally expand, they can account for a substantial fraction of steady state hematopoiesis, termed clonal hematopoiesis of indeterminate potential (CHIP).
“As these HSCs clonally expand, they can account for a substantial fraction of steady state hematopoiesis, termed clonal hematopoiesis of indeterminate potential (CHIP) (Busque et al., 1996; Champion et al., 1997; Vas et al., 2012).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Vas et al., 2012
In some elderly individuals, HSCs acquire oncogenic mutations that allow them to outcompete their neighbors and clonally expand.
“However, in some elderly individuals, HSCs acquire oncogenic mutations that allow them to outcompete their neighbors and clonally expand.”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Vas et al., 2012
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References 26 · Cited by 83
- Authors
- Vas, V., Senger, K., Dörr, K., Niebel, A., & Geiger, H.
- Affiliations
- Universität Ulm (DE)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Geiger, Hartmut
- ORCID
- Geiger, Hartmut
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-08-06
- Volume
- 7
- Issue
- 8
- Pages
- e42080
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3412859
- OpenAlex
- W2038608871
- Cited by
- 83
- References
- 26
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 4 · 2013: 9
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 142, GE2063/1)
- Universität Ulm
- National Institute on Aging (AG040118, R01AG040118)
- National Heart, Lung, and Blood Institute (R01HL076604, HL076604)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK077762, R21DK077762)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- hematopoietic microenvironment, aging, leukemia initiation, hematopoietic progenitor cells, clonal expansion, oligoclonality, monoclonality, hematopoietic niche
- MeSH terms
- Aging, Animals, Cell Separation, Clone Cells, Colony-Forming Units Assay, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred C57BL, Cellular Senescence, Mice, Cellular Microenvironment
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