天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (12): 1295-1299.doi: 10.11958/20181088

• 临床研究 • 上一篇    下一篇

ASXL1突变的髓系肿瘤患者共突变基因谱及其临床意义

滕广帅，王颖韶，徐晶，杜晨霄，王艳，陈亚芳，盛梦瑶，白姣姣，张磊，周圆，杨逢春，白洁    

  1. 1天津医科大学第二医院血液科（邮编300211）；2中国医学科学院血液病医院（血液学研究所）实验血液学国家重点实验室
  • 收稿日期:2018-07-17 修回日期:2018-10-23 出版日期:2018-12-15 发布日期:2019-01-24
  • 通讯作者: 王颖韶 E-mail:1359468328@qq.com
  • 作者简介:血液专题约稿

Spectrum of gene mutation and clinical significance in myeloid malignancy patients with ASXL1 mutation

TENG Guang-shuai,WANG Ying-shao,XU Jing,DU Chen-xiao,WANG Yan,CHEN Ya-fang,SHENG Meng-yao,BAI Jiao-jiao,ZHANG Lei,ZHOU Yuan,YANG Feng-chun, BAI Jie   

  1. 1 Department of Hematology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China; 2 State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College
  • Received:2018-07-17 Revised:2018-10-23 Published:2018-12-15 Online:2019-01-24

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摘要： 目的 探讨具有ASXL1突变的髓系肿瘤患者的共突变基因谱及其临床意义。方法 采用包含112个血液肿瘤相关基因的靶向测序技术对1 335例髓系肿瘤患者进行基因突变检测，筛选出ASXL1突变患者，对这部分患者的共突变基因谱进行分析，并分析其发病特征及预后情况。结果 1 335例髓系肿瘤患者中筛选出138例ASXL1突变阳性患者，包括骨髓增生异常综合征（MDS）52例（37.68%），骨髓增殖性肿瘤（MPN）29例21.01%）、MDS/MPN10例（7.25%），急性髓系白血病（AML）47例（34.06%）。与ASXL1共突变基因谱分析结果显示，96.4%（133例）的患者伴有至少 1 个共突变基因；共突变基因谱中，表观遗传学基因占 55.8%（77/138），信号传导通路相关基因占 65.9%（91/138），转录因子基因占36.9%（51/138），细胞周期与凋亡相关基因占18.8%（26/138）。其中最常见的共突变基因组为RAS（25.4%）、SETBP1（21.7%）、FAT1（18.8%）、CREBBP（15.9%）及TET2（15.2%）。五大共突变基因组中，与ASXL1+RAS-患者相比，ASXL1+RAS+患者预后较差，表现为血红蛋白及血小板减少，染色体核型异常比例升高，生存时间缩短；而ASXL1合并SETBP1、FAT1、CREBBP及TET2突变患者的临床特征和预后差异无统计学意义。结论 ASXL1突变的髓系肿瘤患者常伴随多种基因共突变，其中伴随RAS通路基因共突变患者预后较差。

关键词: 白血病, ASXL1突变, 髓系肿瘤, 二代测序, 共突变

Abstract: Objective To study the spectrum of gene mutation and its clinical significance in myeloid malignancy patients with ASXL1 mutation. Methods The 112-gene targeted sequencing was used to analyze 1 335 patients with myeloid malignancies. The impact of gene mutation on clinical characteristics and prognosis of patients with ASXL1 mutations was analyzed. Results There were 138 (9.2%) patients with ASXL1 mutation including myelodysplastic syndromes (MDS, n=52, 37.68%), myeloproliferative neoplasms (MPN, n=29, 21.01%), MDS/MPN (n=10, 7.25%), and acute myeloid leukemia (AML, n=47, 34.06%). Eighty-nine mutation genes were found in 138 patients, and 96.4% (133) of the patients were accompanied by more than one gene mutation. Among them, epigenetic genes were 55.8% (77 / 138), signal transduction pathway gene, spliceosome 65.9% (91/138), transcription factor 36.9% (51/138), and cell cycle and apoptosis related genes 18.8% (26 / 138). The most common co-mutation genes were RAS 25.4%, SETBP1 21.7%, FAT1 18.8%,CREBBP 15.9% and TET2 15.2%. Compared with patients with ASXL1+RAS-, patients with ASXL1+RAS+ showed a worse prognosis, with decreased hemoglobin and platelet, increased chromosome karyotype abnormality rate, and significantly lower survival. There were no significant differences in the clinical features and prognosis between patients with SETBP1,FAT1, CREBBP and TET2 mutation combined with ASXL1. Conclusion We provide a comprehensive overview of the spectrum, clinical associations and prognostic relevance of gene co-mutations with ASXL1 in patients with myeloid malignancies. Patients with co-mutation of ASXL1 and RAS pathway gene have a worse prognosis.

Key words: leukemia, ASXL1 mutation, myeloid malignancies, next generation sequencing, co-mutation