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目的：探讨急性髓系白血病（AML）基因突变谱及其与首次诱导疗效的关系。方法：回顾性收集2018年1月至2021年12月中山大学附属第三医院收治的AML患者的临床资料，使用二代测序（NGS）技术检测基因突变情况，绘制基因突变谱，分析突变基因之间的共存与互斥关系，探讨基因突变与AML首次诱导疗效的相关性。结果：AML患者140例共检出451个基因突变，突变频率最高的基因分别为CEBPA(20.0%),NPM1(20.0%)和WT1(15.0%)。突变基因的共存与互斥分析显示，NPM1与DNMT3A、TET2、IDH2存在显著的共现关系，且RUNX1与BCOR、CSF3R也存在显著的共存关系。AML首次诱导疗效的影响因素分析显示，患者初诊时血小板计数和TET2突变频率存在显著组间差异（均P<0.05），未缓解组（NR）血小板计数高于完全缓解（CR）组和部分缓解（PR）组，NR组TET2突变频率显著高于CR组。AML伴NPM1突变亚型中发生TET2突变患者CR率显著降低。结论：TET2突变会降低AML伴NPM1突变亚型患者的首次诱导疗效，对于后续治疗方案的选择及长期预后评估具有一定的临床价值。
Abstract：Objective:To investigate the gene mutation spectrum in acute myeloid leukemia(AML)and its relationship with the efficacy of first induction therapy.Methods:The clinical data of AML patients admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2018 to December 2021 were retrospectively collected. Next-generation sequencing(NGS)was used to detect gene mutations,and the gene mutation spectrum were drawed. Co-occurrence and mutual exclusion relationship between mutant genes were analyzed,and the correlation between gene mutations and the first induction efficacy of AML were investigated.Results:A total of 451 mutations were detected in 140 AML patients,while the genes with the highest mutation frequency were CEBPA(20.0%),NPM1(20.0%)and WT1(15.0%). Co-occurrence and mutual exclusion analysis of mutant genes showed that NPM1 had a significant co-occurrence relationship with DNMT3A,TET2 and IDH2;Meanwhile,RUNX1 also has a significant coexistence relationship with BCOR and CSF3R. The analysis of the influencing factors of the first induction efficacy of AML showed that there were significant differences in the count of platelets and the frequency of TET2 mutation at the initial diagnosis(both P<0.05),and the count of platelets of non-remission(NR)group was higher than that of the complete remission(CR)group and the partial remission(PR)group,while the frequency of TET2 mutation in the NR group was significantly higher than that in the CR group. In the subtype of NPM1 mutation of AML,patients with TET2mutation have a lower CR rate.Conclusions:TET2mutation will reduce the first induction efficacy of AML patients with NPM1 mutation subtype,which has certain clinical value for the selection of follow-up treatment regimens and long-term prognosis evaluation.
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基本信息:
中图分类号:R733.71
引用信息:
[1]袁杰铖,蔡晓虹,陈禹欣,等.急性髓系白血病基因突变谱及其与首次诱导疗效的关系[J].广州医科大学学报,2023,51(04):1-8.
2023-08-15
2023-08-15