再生障碍性贫血髓系肿瘤基因突变靶向测序临床研究

张婷; 陈洋; 李瑞鑫; 陈曦; 龙启强; 乔纯; 王琰; 王蓉; 何广胜; 师锦宁; 李建勇

doi:10.13201/j.issn.1004-2806.2021.03.005

再生障碍性贫血髓系肿瘤基因突变靶向测序临床研究

- 1. 南京医科大学附属江宁医院血液内科(南京, 211100);
- 2. 江苏省人民医院南京医科大学第一附属医院血液内科;
- 3. 南京市第二医院东南大学附属第二医院血液内科
基金项目:
江苏省医学重点项目(No:BL2014086)

江苏省普通高校优势学科(No:JX10231801)

南京医科大学科技发展基金一般项目(No:NMUB2019236)

国家中医药管理局行业专项(No:201407001-4)

北京康盟基金会项目(No:WS019E)

详细信息

通讯作者: 何广胜,E-mail:heguangsheng1972@sina.com

中图分类号: R556.5

收稿日期: 2020-10-31

Targeted sequencing of genetic mutations in patients with aplastic anemia

- 1. Department of Hematology, the Affiliated Jiangning Hospital of Nanjing Medical University, Nangjing, 211100, China;
- 2. Department of Hematology, the First Affiliated Hospital of Nanjing Medical University;
- 3. Department of Hematology, the Second Hospital of Dongnan Medical University

More Information

Corresponding author: HE Guangsheng, E-mail: heguangsheng1972@sina.com

Received Date: 31 October 2020

摘要

摘要: 目的:分析常见髓系肿瘤基因突变在再生障碍性贫血(AA)中的发生率和特点,与AA患者的临床特征和免疫抑制治疗(IST)结果的相关性。方法:收集213例AA患者初诊及IST后第6、12、24个月的外周血标本,使用二代基因测序法对34种常见髓系肿瘤基因进行检测,分析基因突变特点与AA患者的临床特征、IST疗效及疾病转化之间的相关性。结果:初诊时32例患者检测到基因突变,突变频率为15.02%,18个基因发生总计34次突变。突变次数最多的前3位基因分别为PIGA 35.29%(12/34)、TET2 14.71%(5/34)、ASXL1 11.76%(4/34);儿童组(0~18岁)、青中年组(18~59岁)及老年组(≥60岁)突变率分别为12.50%(4/32)、13.99%(20/143)和21.05%(8/38);重型AA患者突变发生率显著高于非重型AA患者(20.20%vs 10.53%,P=0.048 7)。环孢菌素治疗组突变发生率低于抗人胸腺细胞免疫球蛋白联合环孢菌素治疗组(0 vs 6.9%,P=0.018)。治疗新出现预后不良基因突变2例,均无效。结论:AA患者的髓系肿瘤基因突变发生与疾病严重程度和治疗措施可能有关,新出现髓系肿瘤相关基因突变可能与疗效不良有关。
- 再生障碍性贫血 /
- 免疫抑制治疗 /
- 环孢菌素 /
- 抗人胸腺细胞免疫球蛋白 /
- 髓系肿瘤基因 /
- 二代基因测序法
Abstract: Objective: To analyze the incidence of common myeloid tumor gene mutation and its correlation with the clinical characteristics as well as immunosuppressive therapy(IST) results in patients with aplastic anemia(AA).Methods: Peripheral blood samples from 213 AA patients were collected at initial diagnosis, and 6, 12, 24 months after IST. A total of 34 common myeloid tumor genes in blood samples were dected by the next-generation gene sequencing(NGS). The association between the results of NGS and the clinical features, efficacy of IST as well as disease transformation of AA patients was elevated.Results: Gene mutations were detected in 32 patients at the time of initial diagnosis, and the mutation frequency was 15.02%. It was found that 18 gene mutated with a total of 34 times. The top three mutations were PIGA(35.29%), TET2(14.71%) and ASXL1(11.76%), respectively. The mutation rates of children group(0-18 years old), young and middle-aged group(18-59 years old) and elderly group(≥60 years old) were 12.50%(4/32), 13.99%(20/143) and 21.05%(8/38), respectively. The mutation rate of SAA patients was significantly higher than that of non SAA patients(20.20%[20/99] vs 10.53%[12/114],P=0.048 7). The mutation rate of cyclosporin treatment group was lower than that of anti-thymocytoglobulin and cyclosporin treatment group(0 vs 6.9%; P=0.018).Conclusion: The occurrence of myeloid tumor gene mutations in AA patients may be related to the severity of the disease and treatment measures, and the new myeloid tumor related gene mutations may be related to poor therapeutic efficacy.
- aplastic anemia /
- immunosuppressive therapy /
- cyclosporine /
- anti-thymocytoglobulin /
- myeloid tumor gene /
- second generation gene sequencing

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