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

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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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Acquired skewing of Lyonization remains stable for a prolonged period in healthy blood donors
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Descriptive and Functional Genomics in Acute Myeloid Leukemia (AML): Paving the Road for a Cure
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“Studies in the 90s measuring X‐inactivation ratios identified a nonrandom X‐ inactivation pattern in blood cells, particularly within the myeloid compartment [33,34].”
Background
Essential thrombocythemia
Harrison, C. N., & Green, A. R. (2003) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(03)00082-0 · Cited by 28
Self-citation
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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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“Such a process might partly explain aberrant results in the absence of appropriate controls (T cells for hematopoietic tissue) [25] as well as the occurrence, in more than 20% of normal elderly women, of a clonal pattern of X chromosome inactivation (clonal granulocytes and polyclonal T lymphocytes) [20].”
Background
Combined landscape of single-nucleotide variants and copy-number alterations in clonal hematopoiesisPreprint
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Self-citation
4 Treatment of polycythaemia vera and essential thrombocythaemia
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“of healthy females over the age of 65 years [27,28].”
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
“Our results are in line with the studies mentioned above, as age-acquired skewed XCI could influence the predisposition and manifestation of aging-related traits, such as hematopoietic malignancy in women [46,48].”
Result
Molecular Pathways in Clonal Hematopoiesis: From the Acquisition of Somatic Mutations to Transformation into Hematologic Neoplasm
Gaulin, C., Kelemen, K., & Yi, C. A. (2022) · Life · doi:10.3390/life12081135 · Cited by 16
A Novel, Essential Control for Clonality Analysis with Human Androgen Receptor Gene Polymerase Chain Reaction
van Dijk, J. P., Heuver, L. H. H., van der Reijden, B. A., Raymakers, R. A. P., de Witte, T., & Jansen, J. H. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64240-x · Cited by 16

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

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