骨髓增生异常综合征患者基因突变与预后的关系  

Relationship between gene mutation and prognosis of patients with myelodysplastic syndrome

作　　者：张小寒 尼罗帕尔·吐尔逊[1] 秦玉婷[1] 赵芳[1] 王欢[1] 江明[1] 郝建萍[1] ZHANG Xiao-han;Niluopaer TUERXUN;QIN Yu-ting;ZHAO Fang;WANG Huan;JIANG Ming;HAO Jian-ping(Hematologic Disease Center,the First Affiliated Hospital of Xinjiang Medical University,Xinjiang Uygur Autonomous Region Institute of Hematology,Urumqi,Xinjiang Uygur Autonomous Region 830011,China)

机构地区：[1]新疆医科大学第一附属医院血液病中心新疆维吾尔自治区血液病研究所,新疆维吾尔自治区乌鲁木齐830011

出　　处：《中华实用诊断与治疗杂志》2022年第4期325-329,共5页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金地区基金(81560027)。

摘　　要：目的 观察骨髓增生异常综合征(myelodysplastic syndrome, MDS)患者基因突变特点,探讨其对患者预后的影响。方法 250例MDS患者均采用5-阿扎胞苷治疗,治疗前应用二代测序技术检测MDS患者骨髓中34种髓系肿瘤相关基因突变情况,分析基因突变特点;根据国际预后积分系统(Revised International Prognostic Scoring System, IPSS-R)分为较低危组(IPSS-R积分≤3.5分)110例和较高危组(IPSS-R积分>3.5分)140例,比较2组基因突变情况;中位随访时间20个月,采用Kaplan-Meier生存曲线分析2组不同基因突变者与未突变者中位生存时间的差异;采用多因素Cox回归分析MDS患者预后不良的影响因素。结果 250例患者中178例发生基因突变,基因突变率为71.2%,其中发生1个基因突变66例,2个基因突变43例,3个基因突变30例,>3个基因突变39例,未发生基因突变72例;基因突变率≥10%的有ASXL1基因突变49例(19.6%),TET2基因突变42例(16.8%),SF3B1基因突变38例(15.2%),BCOR基因突变35例(14.0%),U2AF1基因突变33例(13.2%),DNMT3A基因突变28例(11.2%),TP53基因突变25例(10.0%)。较高危组≥3个基因突变比率(32.86%)及BCOR、U2AF1、TP53基因突变率(19.29%、17.14%、14.29%)均高于较低危组(20.91%、7.27%、8.18%、4.55%)(P<0.05),SF3B1基因突变率(5.00%)低于较低危组(28.18%)(χ^(2)=25.682,P<0.001);较高危组患者表观调节、信号转导、细胞周期与凋亡相关基因突变率(43.57%、20.71%、20.00%)均高于较低危组(30.91%、10.91%、5.45%)(P<0.05),剪切因子基因突变率(25.71%)低于较低危组(37.27%)(χ^(2)=3.861,P=0.049)。较低危组与较高危组TP53基因突变患者中位生存时间(11、22个月)均短于未突变者(45、33个月)(Z=—1.787,P=0.037;Z=—4.986,P<0.001),较低危组SF3B1突变患者中位生存时间(52个月)长于未突变者(41个月)(Z=3.149,P=0.002);2组ASXL1、TET2、U2AF1、DNMT3A、RUNX1基因突变者中位生存时间与未突变者比较差异均无统计学意义(P>0.05)。Objective To observe the features of gene mutation in patients with myelodysplastic syndrome(MDS) and to explore its impact on the prognosis. Methods In 250 MDS patients receiving 5-azacitidine treatment, 34 myeloid tumor-associated mutated genes were detected by next-generation sequencing technology to analyze the gene mutation features. According to the Revised International Prognostic Scoring System(IPSS-R), 250 patients were divided into 110 patients with IPSS-R score ≤3.5(low-risk group) and 140 patients with IPSS-R score >3.5(high-risk group). The gene mutation was compared between two groups. The mean follow-up time was 20 months. Kaplan-Meier survival curve was used to analyze the difference of mean survival time in patients with different gene mutations and those without mutations in two groups. Multivariate Cox regression was used to analyze the influencing factors of poor prognosis of MDS patients. Results In 250 patients, 178 patients were found gene mutations with the detection rate of 71.2%, in which there were 66 patients with 1 mutation, 43 with 2 mutations, 30 with 3 mutations, 39 with >3 mutations and 72 with no mutation. The gene mutations with mutation rate ≥10% included ASXL1 mutation in 49 patients(19.6%), TET2 mutation in 42 patients(16.8%), SF3 B1 mutation in 38 patients(15.2%), BCOR mutation in 35 patients(14.0%),U2AF1 mutation in 33patients(13.2%),DNMT3A mutation in 28patients(11.2%),and TP53mutation in 25patients(10.0%).The percentage of patients with≥3mutations,as well as the mutation rates of BCOR,U2AF1,and TP53 genes were higher in high-risk group(32.86%,19.29%,17.14%,14.29%)than those in low-risk group(20.91%,7.27%,8.18%,4.55%)(P<0.05),and the SF3B1 mutation rate was lower in high-risk group(5.00%)than that in low-risk group(28.18%)(χ^(2)=25.682,P<0.001).The mutation rates of apparent regulation,signal transduction,and cell cycle and apoptosis-related gene mutations were higher in high-risk group(43.57%,20.71%,20.00%)than those in low-risk group(30.91%,10.91%,5.45%)(P<0.05),a

关 键 词：骨髓增生异常综合征 二代测序 基因突变 TP53基因 SF3B1基因 

分 类 号：R551.3[医药卫生—血液循环系统疾病]