Clonal hematopoiesis in donors and long-term survivors of related allogeneic hematopoietic stem cell transplantation
Clonal hematopoiesis in donors and long-term survivors of related allogeneic hematopoietic stem cell transplantation
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DOI：
10.1182/blood.2019003079
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发表时间：
2020-04-30
期刊：
影响因子：
20.3
通讯作者：
Manz, Markus G.
中科院分区：
文献类型：
--
作者：
Boettcher, Steffen;Wilk, C. Matthias;Manz, Markus G.
克隆性造血（CH）与年龄和髓系恶性肿瘤风险、心血管风险和全因死亡率增加相关。我们在同一个体的造血干细胞（HSC）暴露于不同程度的增殖应激和环境的环境中测试CH，即在异基因造血干细胞移植（allo-HSCT）的长期存活者及其各自的相关供体（n = 42个供体-受体对）中。自allo-HSCT以来的中位随访时间为16年（范围，10-32年），我们在84名研究参与者中的23名（27.4%）中发现了35个突变。10/42名供体（23.8%）和13/42名受体（31%）患有CH。CH与供体和受体年龄较大有关。我们确定了5例供者移植的CH，1例供者和受者均进展为骨髓增生异常综合征。5例中有4例受者的克隆大小比供体增加。我们进一步对CH患者的造血系统进行了如下特征：（1）CH在髓系细胞中持续存在，但在B和T细胞中的表达率不同：（2）在CH多突变个体中，集落形成单位（CFU）显示克隆进化或多个独立克隆;（3）粒细胞端粒缩短提示受者造血干细胞增殖史较供者增加20年，CH与非CH CFU中的端粒长度显示不同的模式。这项研究提供了对相同的人类HSC的长期行为和不同增殖条件下各自的CH发展的见解。
Clonal hematopoiesis (CH) is associated with age and an increased risk of myeloid malignancies, cardiovascular risk, and all-cause mortality. We tested for CH in a setting where hematopoietic stem cells (HSCs) of the same individual are exposed to different degrees of proliferative stress and environments, ie, in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their respective related donors (n = 42 donor-recipient pairs). With a median follow-up time since allo-HSCT of 16 years (range, 10-32 years), we found a total of 35 mutations in 23 out of 84 (27.4%) study participants. Ten out of 42 donors (23.8%) and 13 out of 42 recipients (31%) had CH. CH was associated with older donor and recipient age. We identified 5 cases of donor-engrafted CH, with 1 case progressing into myelodysplastic syndrome in both donor and recipient. Four out of 5 cases showed increased clone size in recipients compared with donors. We further characterized the hematopoietic system in individuals with CH as follows: (1) CH was consistently present in myeloid cells but varied in penetrance in B and T cells; (2) colony-forming units (CFUs) revealed clonal evolution or multiple independent clones in individuals with multiple CH mutations; and (3) telomere shortening determined in granulocytes suggested similar to 20 years of added proliferative history of HSCs in recipients compared with their donors, with telomere length in CH vs non-CH CFUs showing varying patterns. This study provides insight into the long-term behavior of the same human HSCs and respective CH development under different proliferative conditions.