Acquired skewing of X-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age
Acquired skewing of X-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age
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DOI：
10.1046/j.1365-2141.1997.2573078.x
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发表时间：
1997-09-01
影响因子：
6.5
通讯作者：
Linch, DC
中科院分区：
文献类型：
--
作者：
Gale, RE;Fielding, AK;Linch, DC
老年女性的白色血细胞中更常见的X染色体失活模式（XCIP）偏斜;本研究旨在确定这种情况是否发生在髓系或淋巴系。在来自80名> 75岁女性的纯化中性粒细胞和T细胞中分析XCIP，并将结果与23份脐带血和94份年轻成人血液样品进行比较。脐带血和年轻成人血细胞中的XCIP偏斜程度相似，其中3-4%具有>90%的一个等位基因表达。老年女性中性粒细胞的偏斜显著增加，其中33%具有>90%的一个等位基因表达（P < 0.0001）。只有9%的老年人T细胞样本存在极端倾斜，通过PCR分析TCR γ基因，没有发现T细胞克隆性的证据。老年人骨髓细胞中XCIP的高水平获得性偏斜表明，随着时间的推移，干细胞的使用会发生变化，一些原始干细胞会随机丢失。这对XCIP分析在老年人骨髓恶性肿瘤诊断和造血干细胞基因治疗中的应用具有重要意义。
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 allele. Skewing was markedly increased in the neutrophils of elderly females, with 33% having >90% expression of one allele (P < 0.0001). Extreme skewing was present in only 9% of the elderly T-cell samples and no evidence of T-cell clonality was found by PCR analysis of the TCR gamma gene. The high level of acquired skewing of the XCIPs in myeloid cells of the elderly suggests that with time there is a change in stem cell usage with stochastic loss of some of the original stem cells. This has ma)or implications for the use of XCIP analysis in the diagnosis of myeloid malignancies in the elderly and for gene therapy into haemopoietic stem cells.