The DOI matches its Crossref record.
Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes
Abstract
Studies of X chromosome inactivation patterns are central to many aspects of our understanding of the pathogenesis of haematological malignancies. In patients with myeloproliferative disorders and myelodysplastic syndromes the demonstration of skewed X inactivation patterns in multiple haemopoietic lineages has been taken to indicate a stem cell origin for these groups of diseases. However, stem cell depletion or selection pressures can also produce skewed X inactivation patterns and might increase with age. We have therefore used the HUMARA assay to study X inactivation patterns of elderly patients with myeloproliferative disorders together with an age-matched control group of normal elderly women. A clonal pattern (clonal granulocytes and polyclonal T cells) was observed in 23.1% of normal women and 63.4% of patients with myeloproliferative disorders. This is the first report of X inactivation patterns in purified subpopulations of blood cells in normal elderly women. These results have three significant implications. Firstly, the finding of clonal granulocytes and polyclonal T cells in normal elderly women is likely to reflect age-related stem cell depletion or selection pressures. Secondly, the demonstration of clonal granulocytes and polyclonal T cells is not a useful diagnostic marker for myeloproliferative disorders or myelodysplastic syndromes in elderly women. Thirdly, our data raise the possibility that clonal blood cell patterns may precede rather than follow mutations which subsequently give rise to myelodysplastic or myeloproliferative phenotypes.
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In the citing paper
“during aging, blood cells are derived from fewer and fewer stem cells.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [80]
In the citing paper
“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 Champion et al., 1997
In the citing paper
“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 Champion et al., 1997
In the citing paper
“Importantly, non-random XCI in blood cells was observed to increase in frequency with age, although the underlying mechanism was unclear 19.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [19]
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Metadata
- Authors
- Champion, K. M., Gilbert, J. G. R., Asimakopoulos, F. A., Hinshelwood, S., & Green, A. R.
- Affiliations
- University of Cambridge (GB)
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 1997-06
- Volume
- 97
- Issue
- 4
- Pages
- 920-926
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W2028835250
- Cited by
- 171
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 9 · 2021: 10 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- X chromosome inactivation, myeloproliferative neoplasms, myelodysplastic syndrome, older women, polyclonal T cells, HUMARA assay, stem cell depletion
- MeSH terms
- Aged, Aged, 80 and over, Clone Cells, Female, Granulocytes, Hematopoiesis, Humans, Middle Aged, Myelodysplastic Syndromes, Myeloproliferative Disorders, T-Lymphocytes, X Chromosome, Polymerase Chain Reaction
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