1997
DOI: 10.1046/j.1365-2141.1997.2573078.x
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Acquired skewing of X‐chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age

Abstract: Summary.More frequent skewing of X-chromosome inactivation patterns (XCIPs) occurs in the white blood cells of elderly females; this study was performed to determine whether this occurs in myeloid or lymphoid lineages. XCIPs were analysed in purified neutrophils and T cells from 80 females > 75 years and the results were compared with 23 cord blood and 94 younger adult blood samples. The degree of XCIP skewing in cord blood and younger adult blood cells was similar, with 3-4% having > 90% expression of one all… Show more

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Cited by 227 publications
(197 citation statements)
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“…2C-2) Psup = 54% indicates no skewing, similar to the HUMARA DNA studies in the whole blood (Psup = 40%), implying that the presence in whole blood of a significant number of T cells derived from earlier stem cells, before the acquired skewing occurred, masked the high XCI skewing in the granulocytes. These results are in accordance to previous reports showing that skewing was markedly increased in older women's granulocytes, but not in T cells [11][12][13]. As lymphocytes have a long circulatory lifetime, these data are consistent with XCI skewing developing with age, implying that HUMARA assay in whole blood is not reliable to quantify the XCI skewing in older women.…”
Section: Humara Assayssupporting
confidence: 90%
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“…2C-2) Psup = 54% indicates no skewing, similar to the HUMARA DNA studies in the whole blood (Psup = 40%), implying that the presence in whole blood of a significant number of T cells derived from earlier stem cells, before the acquired skewing occurred, masked the high XCI skewing in the granulocytes. These results are in accordance to previous reports showing that skewing was markedly increased in older women's granulocytes, but not in T cells [11][12][13]. As lymphocytes have a long circulatory lifetime, these data are consistent with XCI skewing developing with age, implying that HUMARA assay in whole blood is not reliable to quantify the XCI skewing in older women.…”
Section: Humara Assayssupporting
confidence: 90%
“…Several reports using the HUMARA assay show that the incidence of skewing is relatively low at birth and in adult non-hematopoietic tissues, but higher and agedependent in hematopoietic cells, with 30-40% of healthy elderly women reported to have skewing (greater than 75% expression of one parental X chromosome) [5][6][7][8][9][10][11][12]. T lymphocytes show less evidence of skewing with age than neutrophils, presumably reflecting the neutrophils' short half-life, whereas T lymphocytes are long-living cells, and in consequence, some T cells are produced near the time of study but others are derived from earlier stem cells [11][12][13]. This agerelated skewing in blood cells has been attributed to clonality as a consequence of hematopoietic stem cell senescence [5,7,9].…”
mentioning
confidence: 99%
“…Increasing age is accompanied by changes to the hematopoietic stem cell (HSC) compartment, a process known as myeloid shift, with a bias towards the myeloid lineage at the expense of the lymphoid lineage 9 . In addition, acquired skewing of X-chromosome inactivation patterns (XCIP) in elderly women suggests that there is a reduction in stem cell usage over time that might in principle be stochastic or driven by subclinical clonal expansion 10 . These combined factors may help to explain the higher frequency of myeloid neoplasia in the elderly population.…”
Section: Detection Of Leukemia-associated Mutations In Peripheral Blomentioning
confidence: 99%
“…To investigate the presence of mutations in elderly populations further, we studied two independent cohorts, (i) the Uppsala Longitudinal Study of Adult Men (ULSAM), an ongoing epidemiologic study of all available men born between 1920-24 in Uppsala County, Sweden that have been analyzed by SNP arrays 1,4 and (ii) 56 elderly women with normal blood counts and paired DNA from both neutrophils and T cells 10 .…”
Section: Detection Of Leukemia-associated Mutations In Peripheral Blomentioning
confidence: 99%
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