阵发性夜间血红蛋白尿（PNH）的突变分析。
Analysis of mutations in paroxysmal nocturnal hemoglobinuria (PNH).
作者信息
Lobry Camille, Bains Ashish, Zamechek Leah B, Ibrahim Sherif, Aifantis Iannis, Araten David J
机构信息
1Institut National de la Santé et de la Recherche Medicale (INSERM) U1170, Institut Gustave Roussy, 94805 Villejuif, France.
2Pathology and Laboratory Medicine, Temple University, 3401 North Broad Street, Philadelphia, PA 19140 USA.
出版信息
Exp Hematol Oncol. 2019 Aug 21;8:17. doi: 10.1186/s40164-019-0142-0. eCollection 2019.
BACKGROUND
Large clonal populations of cells bearing - mutations are the sine qua non of PNH, but the - mutation itself is insufficient for clonal expansion. The association between PNH and aplastic anemia supports the immune escape model, but not all PNH patients demonstrate a history of aplasia; therefore, second genetic hits driving clonal expansion have been postulated. Based on the previous identification of mutations in patients with a myeloproliferative/PNH overlap syndrome, we considered as a candidate gene in which mutations might be contributing to clonal expansion.
METHODS
Here we sequenced the and genes in 19 patients with large PNH clones.
RESULTS
We found one patient with a novel somatic nonsense mutation in in multiple hematopoietic lineages, which was detectable upon repeat testing. This patient has had severe thromboses and has relatively higher peripheral blood counts compared with the other patients-but does not have other features of a myeloproliferative neoplasm.
CONCLUSIONS
We conclude that mutations in may contribute to clonal expansion in exceptional cases of PNH.
背景
携带-突变的大量克隆细胞群体是阵发性睡眠性血红蛋白尿症（PNH）的必要条件，但-突变本身不足以导致克隆性扩增。PNH与再生障碍性贫血之间的关联支持免疫逃逸模型，但并非所有PNH患者都有再生障碍病史；因此，有人推测存在驱动克隆性扩增的第二次基因打击。基于先前在骨髓增殖性/PNH重叠综合征患者中鉴定出的-突变，我们认为-是一个候选基因，其中的突变可能促成克隆性扩增。
方法
在此，我们对19例具有大PNH克隆的患者的-和-基因进行了测序。
结果
我们发现1例患者在多个造血谱系的-基因中存在一种新的体细胞无义突变，重复检测时可检测到。该患者发生过严重血栓形成，与其他患者相比外周血细胞计数相对较高，但不具有骨髓增殖性肿瘤的其他特征。
结论
我们得出结论，在PNH的特殊病例中，-基因的突变可能促成克隆性扩增。
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