Clonal haemopoiesis in normal elderly women: Implications for the myeloproliferative disorders and myelodysplastic syndromes
Clonal haemopoiesis in normal elderly women: Implications for the myeloproliferative disorders and myelodysplastic syndromes
复制标题
DOI：
10.1046/j.1365-2141.1997.1933010.x
复制
发表时间：
1997-06-01
影响因子：
6.5
通讯作者：
Green, AR
中科院分区：
文献类型：
--
作者：
Champion, KM;Gilbert, JGR;Green, AR
X染色体失活模式的研究是我们理解血液系统恶性肿瘤发病机制的许多方面的核心。在骨髓增生性疾病和骨髓增生异常综合征患者中，多个造血谱系中的偏斜X失活模式的证明已被用于指示这些疾病组的干细胞起源。然而，干细胞耗竭或选择压力也会产生偏斜的X失活模式，并可能随着年龄的增长而增加。因此，我们使用HUMARA分析来研究患有骨髓增生性疾病的老年患者以及年龄匹配的正常老年女性对照组的X失活模式。（克隆粒细胞和多克隆T细胞）在23.1%的正常女性和63.4%的骨髓增生性疾病患者中观察到，这是首次报道正常老年妇女血细胞纯化亚群的X失活模式。这些结果有三个重要意义：第一，在正常老年妇女中发现克隆粒细胞和多克隆T细胞可能反映了年龄相关的干细胞耗竭或选择压力。其次，克隆性粒细胞和多克隆性T细胞的表现不是老年妇女骨髓增生性疾病或骨髓增生异常综合征的有用诊断标志物。第三，我们的数据提出了克隆血细胞模式可能先于而不是跟随突变，随后引起骨髓增生异常或骨髓增生性表型的可能性。
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.