再生障碍性贫血（AA）是一种潜在致命的骨髓衰竭综合症，其特征是造血干/祖细胞匮乏、不同程度的细胞减少和骨髓间质脂肪浸润。最新的基因组研究揭示了体细胞突变与AA患者髓系癌症之间的联系。目前这些突变对AA患者的影响尚不确定。我们对279例AA患者和174例骨髓增生异常综合症（MDS）患者进行了回顾性研究，并使用下一代测序（NGS）在他们的骨髓细胞中进行了22个基因的靶向测序。分析了体细胞突变与预后相关性和治疗反应。在279例AA患者中，25例（9.0％）患者存在体细胞突变，20例（7.2％）患者存在一种突变。最常见的基因突变是ASXL1（3.2％的患者）、DNMT3A（1.8％）和TET2（1.8％）。在MDS组中，174例患者中有120例（69.0％）存在体细胞突变，其中81例患者（46.6％）有多个突变。最常见的基因突变是U2AF1（24.7％的患者）、ASXL1（18.4％）和TP53（13.2％）。与MDS患者相比，AA患者存在较低频率的体细胞突变，且多数只有一种突变。同样地，AA患者中位变异等位基因频率低于MDS患者（6.9％与28.4％）。在突变（SM）组中，3个月和6个月的整体反应分别为37.5％和66.7％。此外，与未发现体细胞突变（N-SM）组相比，并没有显著差异。在2年的随访期间，SM组中发生了4例（20％）死亡，N-SM组中发生了40例（18.1％），两组之间的总生存和事件无进展生存没有显著差异。我们的数据表明，在NGS中只有少数AA患者检测到与髓系肿瘤相关的体细胞突变。AA和MDS患者具有不同的基因突变模式。与MDS相比，AA患者的体细胞突变特征是较低的突变频率、主要是一种突变和较低的突变等位基因负担中位数。体细胞突变是老年人中常见的发现，并且随着年龄的增加而增加。血小板计数影响了三个月的治疗反应，而铁蛋白水平影响了六个月的结果，而体细胞突变与治疗反应或长期生存无关。但是，我们突变患者的队列很小，这个结果需要进一步用大样本确认。©2023年作者。

Aplastic anemia (AA) is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells and progenitor cells with varying degrees of cytopenia and fatty infiltration of the bone marrow space. Recent advances in genomics have uncovered a link between somatic mutations and myeloid cancer in AA patients. At present, the impact of these mutations on AA patients remains uncertain. We retrospectively investigated 279 AA patients and 174 patients with myelodysplastic syndromes (MDS) and performed targeted sequencing of 22 genes on their bone marrow cells using next-generation sequencing (NGS). Associations of somatic mutations with prognostic relevance and response to treatment were analyzed. Of 279 AA patients, 25 (9.0%) patients had somatic mutations, and 20 (7.2%) patients had one mutation. The most frequently mutated genes were ASXL1(3.2% of the patients), DNMT3A (1.8%) and TET2 (1.8%). In the MDS group, somatic mutations were detected in 120 of 174 (69.0%) patients, and 81 patients (46.6%) had more than one mutation. The most frequently mutated genes were U2AF1 (24.7% of the patients), ASXL1 (18.4%) and TP53 (13.2%). Compared with MDS patients, AA patients had a significantly lower frequency of somatic mutations and mostly one mutation. Similarly, the median variant allele frequency was lower in AA patients than in MDS patients (6.9% vs. 28.4%). The overall response of 3 and 6 months in the somatic mutation (SM) group was 37.5% and 66.7%, respectively. Moreover, there was no significant difference compared with the no somatic mutation (N-SM) group. During the 2-years follow-up period, four (20%) deaths occurred in the SM group and 40 (18.1%) in the N-SM group, with no significant difference in overall survival and event-free survival between the two groups. Our data indicated that myeloid tumor-associated somatic mutations in AA patients were detected in only a minority of patients by NGS. AA and MDS patients had different gene mutation patterns. The somatic mutations in patients with AA were characterized by lower mutation frequency, mostly one mutation, and lower median allelic burden of mutations than MDS. Somatic mutations were a common finding in the elderly, and the frequency of mutations increases with age. The platelet count affected the treatment response at 3 months, and ferritin level affected the outcome at 6 months, while somatic mutations were not associated with treatment response or long-term survival. However, our cohort of patients with the mutation was small; this result needs to be further confirmed with large patient sample.© 2023. The Author(s).