Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes

Champion, Kim M.; Gilbert, James G. R.; Asimakopoulos, Fotios A.; Hinshelwood, Stephen; Green, Anthony R.

doi:10.1046/j.1365-2141.1997.1933010.x

Cited by 174Acute Myeloid Leukemia ResearchMyeloproliferative Neoplasms: Diagnosis and TreatmentHematopoietic Stem Cell Transplantation

Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes

Champion, Kim M., Gilbert, James G. R., Asimakopoulos, Fotios A., Hinshelwood, Stephen, Green, Anthony R.·1997·British Journal of Haematology

DOI 10.1046/j.1365-2141.1997.1933010.x

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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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With aging, blood cells come from fewer and fewer stem cells.
“during aging, blood cells are derived from fewer and fewer stem cells.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [80]
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 Champion et al., 1997
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 Champion et al., 1997
Non-random X-chromosome inactivation in blood cells increases in frequency with age.
“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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“…were (i) to be aged1 < 62 years; this age limit was chosen to reduce the likelihood of skewed XCIP, the frequency of which is increased in older subjects (Champion et al, 1997; Mitterbauer et al, 1999), and, (ii) to have received any kind of chemotherapy, including interferon, in the last 6 months.”
Background
Clonality analysis using X-chromosome inactivation patterns by HUMARA-PCR assay in female controls and patients with idiopathic thrombocytosis in Taiwan
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Background
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Self-citation
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Background
Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
Nicolì, V., Tabano, S. M., Colapietro, P., Maestri, M., Ricciardi, R., Stoccoro, A., Fontana, L., Guida, M., Miozzo, M. R., Coppedè, F., et al. (2022) · Genes · doi:10.3390/genes13040696 · Cited by 16 · see citing works
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Result
Molecular Pathways in Clonal Hematopoiesis: From the Acquisition of Somatic Mutations to Transformation into Hematologic Neoplasm
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A Novel, Essential Control for Clonality Analysis with Human Androgen Receptor Gene Polymerase Chain Reaction
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Authors: Champion, K. M., Gilbert, J. G. R., Asimakopoulos, F. A., Hinshelwood, S., & Green, A. R.
Affiliations: University of Cambridge (GB)
ORCID: Gilbert, James G. R.
Green, Anthony R.
Venue: British Journal of Haematology
Publisher: Wiley
Published: 1997-06
Volume: 97
Issue: 4
Pages: 920-926
ISSN: 0007-1048 (ISSN-L)
1365-2141
DOI: 10.1046/j.1365-2141.1997.1933010.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2341 d)
Locations: British Journal of Haematology (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Health Sciences › Medicine › Genetics › 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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Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes

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