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DTAS基因突变对初诊急性髓系白血病患者预后的影响

Implication of DTAS gene mutation on prognosis in newly diagnosed patients with acute myeloid leukemia
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摘要 目的探讨DTAS基因(DNMT3A基因、TET2基因、ASXL1基因、SRSF2基因)突变对初诊急性髓系白血病(AML)患者生存期的影响。方法收集2018年1月1日至2021年10月31日于徐州医科大学附属医院血液科接受二代测序检测(NGS)的163例AML患者的临床一般资料,包括患者的身高、体重、性别、年龄、骨髓原始细胞比例、诱导缓解方案、是否移植、外周血指标等进行回顾性分析。其中男88例,女75例,年龄48(33,59)岁。根据患者二代测序资料,将有上述4个基因任一突变者分为DTAS基因突变组,反之为无DTAS基因突变组。同时纳入40名健康对照研究DTAS基因突变与粒淋比和淋单比之间的关系。通过Kaplan-Meier法及Cox回归模型分析生存与预后指标。结果163例患者中,检出DTAS基因突变的患者50例(30.7%),未检出DTAS基因突变的患者113例(69.3%)。在50例DTAS基因突变的患者中,其中≥2个突变的患者有8例(16%),DTAS基因中有任一基因突变的患者有42例(84%)。DTAS基因突变组患者年龄较大、欧洲白血病网预后分层较差、缓解持续时间较短、诱导化疗后28 d重度骨髓抑制程度所占比例[21(61.8%)比31(34.8%)]较高(χ^(2)=7.313,P=0.007),治疗后达完全缓解时,淋单比值较低,且低于健康对照组(Z=4.935,P<0.001)。Kaplan-Meier生存分析结果显示,DTAS基因突变组的总生存时间和无事件生存时间均低于无DTAS基因突变组(P均<0.01)。DTAS基因突变组的中位OS时间为21(95%CI 16.63~25.37)个月,低于无DTAS基因突变组的43(95%CI 33.01~52.99)个月(P=0.003,HR=2.041)。多因素Cox回归分析显示,DTAS基因突变是影响总生存时间的独立危险因素(HR=2.041,95%CI 1.285~3.244,P=0.003)。结论DTAS基因突变不影响AML患者诱导化疗后血象恢复时间,但DTAS基因突变患者缓解持续时间较短。DTAS基因突变提示预后不良,是影响OS的独立危险因素。 Objective To investigate the influence of DTAS gene mutations(DNMT3A,TET2,ASXL1,SRSF2)on survival of newly diagnosed acute myeloid leukemia(AML)patients.Methods A retrospective analysis of 163 patients with next-generation sequencing(NGS)data in the hematology Department of Affiliated Hospital of Xuzhou Medical University from January 1,2018 to October 31,2021 was performed.Clinical data of patients were collected and analyzed including patient′s height,weight,gender,age,bone marrowblast ratio,induction chemotherapy regimen,transplantation or not,complete blood count,etc.There were 88 males and 75 females with a median age of 48(4-81)years.According to the next-generation sequencing data,patients with any mutation of the above four genes were divided into the DTAS gene mutation group,and vice versa,they were divides into non-DTAS gene mutation group.The Kaplan-Meier method and Cox proportional risk model were used to analyze survival and prognosis.Results Among 163 patients,DTAS gene mutation was detected in 50 patients(30.7%),and not in 113patients(69.3%).Among the 50 patients with DTAS genemutations,8 cases(16%)had≥2 mutations and 42 cases(84%)had any gene mutation in DTAS.In the DTAS gene mutation group,the patients were older,the stratification of the European leukemia network(ELN)was poor,the duration of remission was shorter,the proportion of sever myelosuppression degree was higher(61.8%vs 34.8%)at day28 after induction chemotherapy,and the lymphocyte-monocyte ratio was lower than that of the healthy control group when CR was reached after treatment.The results of K-M survival analysis showed that the overall survival(OS)time(P=0.003)and event-free survival(EFS)(P=0.008)time of the DTAS gene mutant were significantly shorter than those of the non-DTAS gene mutated group.The medianOS timein theh DTAS gene mutations was significantly shorter than that in the non-DTAS gene mutated group(P=0.003,HR=2.041)[21(95%CI 16.63-25.37)months vs 43(95%CI 33.01-52.99)months].The results of multivariate COX analysis revealed that DTAS gene mutations was an independent risk facror forOS time(HR=2.041,95%CI:1.285-3.244,P=0.003)in AML patients.Conclusion DTAS gene mutation does not affect the hematopoietic recovery time after induction chemotherapy,but the duration of remission is shorter in the DTAS gene mutations group.DTAS gene mutations indicate a poor prognosis,which is an independent risk factor for OS.
作者 刘俸安 张雅楠 朱静静 梁秀丽 王雪 徐开林 程海 Liu Feng′an;Zhang Ya′nan;Zhu Jingjing;Liang Xiuli;Wang Xue;Xu Kailin;Cheng Hai(Department of Hematology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221002,China)
出处 《中华检验医学杂志》 CAS CSCD 北大核心 2023年第12期1281-1290,共10页 Chinese Journal of Laboratory Medicine
关键词 急性髓系白血病 二代测序检测 血液学恢复 预后 Acute myeloid leukemia Next-generation sequencing Hematopoietic recovery Prognosis
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