Blood:allo-HSCT后的长期存活者及其供体的克隆造血分析

2020-03-21 MedSci原创 MedSci原创

克隆造血(CH),包括供体移植性CH,在供体和allo-HSCT后的长期存活者中非常普遍。CH克隆在造血系统的不同层次上不断扩展,并能进化为亚克隆。

克隆造血(CH)与年龄、骨髓恶性肿瘤风险、心血管风险和全因死亡率升高有关。研究人员检测了同一个体的暴露在不同程度的增殖应激和环境下的造血干细胞(HSCs)的CH情况(通过对102个基因进行二代DNA测序来定义CH:在粒细胞中,VAF≥0.01),如异基因造血干细胞移植(allo-HSCT)的长期存活者及其供体(42对供-受体)

allo-HSCT后的中位随访时间为16年(范围10-32年),研究人员在23位(27.4%)受试者中共检测到35个突变。10位(23.8%)供体和12位(31%)受体存在CH。CH与供体和受体的年纪较大有关。研究人员鉴别出5例供体移植性CH,其中有一例的供体和受体均发展成了骨髓增生异常综合征。与供者相比,4/5的受者的克隆大小增加。

研究人员进一步描述了CH患者的造血系统:1)CH在骨髓细胞中始终存在,但在B细胞和T细胞中的外显率不同;2)克隆形成单位(CFUs)显示,在携带多个CH突变个体中存在克隆进化或多个独立克隆;3)虽然粒细胞端粒缩短表明,受体的造血干细胞较供体增加了大约20年的增殖历史,但CH和非CH CFUs的端粒长度表现出不同的模式。

本研究为研究同一个人的造血干细胞在不同增殖条件下的长期行为及不同的CH发展提供了思路。

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    2020-05-02 aids221
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    2020-07-27 feather85
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    2020-12-23 sjq035
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    2020-03-23 膀胱癌
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    2020-03-23 俅侠
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