Clonal PIGA mosaicism and dynamics in paroxysmal nocturnal hemoglobinuria.
Clonal PIGA mosaicism and dynamics in paroxysmal nocturnal hemoglobinuria.
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DOI：
10.1038/s41375-018-0138-5
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发表时间：
2018-11
期刊：
影响因子：
11.4
通讯作者：
Maciejewski JP
中科院分区：
文献类型：
--
作者：
Clemente MJ;Przychodzen B;Hirsch CM;Nagata Y;Bat T;Wlodarski MW;Radivoyevitch T;Makishima H;Maciejewski JP
简要通讯2507，在免疫介导的骨髓衰竭的情况下，提供比其他未受影响的造血干细胞生长和/或存活的优势[3，4][5]解释PNH与再生障碍性贫血(AA)的独特联系。最近，在PNH克隆中发现了PIGA以外的其他基因突变，这为PNH克隆的内在扩张驱动提供了一个解释，无论或在最初的免疫逃逸发生之后[6]。在健康个体中发现了多个PIGA突变，频率非常低[7]，在偶尔出现的PNH患者的孤立报告中也是如此[8，9]，因此观察没有导致认识到寡克隆性疾病起源的现象可能是普遍存在的，并可能对PNH的发病机制至关重要。PIGA突变细胞在工程动物模型中不能扩增[10]，这表明PNH克隆进化需要额外的许可条件和因素。利用PIGA基因的下一代测序(NGS)和流式细胞仪的细胞分选，我们的目标是确定是否可以改进PIGA突变克隆检测并深入了解PNH克隆动态
Brief Communication 2507 to offer a growth and/or survival advantage over other unaffected HSCs [3, 4] in the context of immune-mediated bone marrow failure [5] explaining the unique association of PNH with aplastic anemia (AA). Recently, additional mutations in genes other than PIGA were identified in PNH clones, offering an explanation for intrinsic expansion drive of PNH clones irrespective of or after the initial immune escape occurred [6]. Multiple PIGA mutations have been discovered at very low frequencies in healthy individuals [7], as well as in isolated reports of occasional PNH patients [8, 9] and thus observation did not lead to the appreciation that the phenomenon of an oligoclonal disease origin may be ubiquitous and potentially essential for the pathogenesis of PNH. PIGA mutant cells fail to expand in engineered animal models [10], suggesting that additional permissive conditions and factors are required for PNH clone evolution. Using next generation sequencing (NGS) of the PIGA gene and cell sorting by flow cytometry, our goal was to determine if we could improve PIGA mutant clone detection and gain insight into PNH clonal dynamics
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DOI：
10.1038/nrdp.2017.28
发表时间：
2017-05-18
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Hill A;DeZern AE;Kinoshita T;Brodsky RA
通讯作者：
Brodsky RA
影响因子：
20.3
作者：
Endo, M;Ware, RE;Parker, CJ
通讯作者：
Parker, CJ
影响因子：
20.3
作者：
Kawagoe, K;Kitamura, D;Takeda, J
通讯作者：
Takeda, J
影响因子：
15.9
作者：
Shen, Wenyi;Clemente, Michael J.;Makishima, Hideki
通讯作者：
Makishima, Hideki
影响因子：
6.5
作者：
Maciejewski, JP;Rivera, C;Young, NS
通讯作者：
Young, NS