急性淋巴细胞白血病基因突变的DNA测序结果分析

Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing

目的:分析成人急性淋巴细胞白血病(ALL)患者的基因突变特征及其意义。方法:收集134例初治成人ALL患者的临床资料及16种基因突变的DNA测序结果,统计分析基因突变特征及其临床意义。结果:134例ALL患者中,31例(23.13%)检测到基因突变,其中114例B-ALL患者中检测到19例(16.67%),19例T-ALL患者中检测到11例(57.89%)及1例T/B双表型ALL,T-ALL基因突变发生率显著高于B-ALL(χ^2=13.574,P<0.01)。共检测到12种基因突变,突变率从高到低依次为IL7R、NOTCH1、FLT3、TP53、FBXW7、PAX5、IKZF1、CREBBP、JAK3、JAK1、PHF6、PTEN。108例非移植可随访患者中,基因突变组(23例,21.30%)与无突变组(85例,78.70%)的1年总生存率(49.7%vs 67.4%)与中位无复发生存时间(214 d vs 260 d)差异均无统计学意义。NOTCH1基因突变组(4例,3.77%)与无突变组(102例,96.23%)的1年生存率差异有统计学意义(50.0%vs 65.8%,χ^2=9.840,P<0.01)。结论:成人ALL患者可能存在多种基因突变,其中IL7R、NOTCH1基因突变最常见,NOYCH1基因突变可能提示预后不良,基因突变检测有助于理解ALL发病机制及评估成人ALL患者的预后。

Objective:To analyze the characteristics of gene mutation in adult ALL and its clinical significance.Methods:Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected.The characteristic of gene mutation and clinical significances were statistically analyzed.Results:In 31 cases of 134 ALL cases(23.13%)the gene mutations were detected as follows:19 cases of 114 B-ALL cases(16.67%),11 cases of 19 T-ALL cases(57.89%)and 1 case of T/B-ALL.The incidence of T-ALL gene mutation was significantly higher than that of B-ALL(χ^2=13.574,P<0.01).Twelve gene mutations were found,and the mutation rates was IL7R,NOTCH1,FLT3,TP53,FBXW7,PAX5,IKZF1,CREBBP,JAK3,JAK1,PHF6 and PTEN from high to low.Among 108 non-transplantable follow-up patients there was no significant difference in 1-year overall survival rate(49.7%vs 67.4%)and median non-recurrence survival time(214 days vs 260 days)between the gene mutation group(23 cases,21.30%)and the non-mutation group(85 cases,78.70%).There was a significant difference in 1-year survival rate between NOTCH1 mutation group(4 cases,3.77%)and non-mutation group(102 cases,96.23%)(50.0%vs 65.8%,χ^2=9.840,P<0.01).Conclusion:There may be multiple gene mutations in adult ALL patients.IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis.Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.