伴TP53基因异常的急性白血病患者的临床特征和疗效分析  

Clinical characteristics and therapeutic effect of TP53 variant in patients with acute leukemia

作　　者：米瑞华 郭珍 刘雯 胡杰英 范瑞华 陈琳 刘佳 魏旭东 Mi Ruihua;Guo Zhen;Liu Wen;Hu Jieying;Fan Ruihua;Chen Lin;Liu Jia;Wei Xudong(Department of Hematopathy,the Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou,Henan 450008,China;Central Laboratory,the Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou,Henan 450008,China)

机构地区：[1]郑州大学附属肿瘤医院血液科,450008 [2]郑州大学附属肿瘤医院中心实验室,450008

出　　处：《中华医学遗传学杂志》2021年第10期955-960,共6页Chinese Journal of Medical Genetics

基　　金：河南省科技厅科技攻关项目(202102310365)。

摘　　要：目的探讨伴TP53基因异常的急性白血病(acute leukemia,AL)患者的临床特征及预后。方法分析经二代测序(next-generation sequencing,NGS)技术检测到的44例伴基因异常的AL患者的临床资料。采用包含108种白血病相关基因的测序技术进行变异分析;常规R显带技术进行核型分析。分析44例伴TP53基因变异的AL患者的临床特征、细胞遗传学、基因变异和疗效及生存情况。结果伴TP53基因变异的急性髓系白血病(acute myeloid leukemia,AML)患者的中位年龄(46岁)高于急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者(17.5岁),且骨髓原始细胞中位数前者(40.5%)低于后者(89.2%),差异均具有统计学意义(P<0.01)。共检出异常核型28例,其中复杂核型25例,16例为单体核型,14例存在-17/17p-。TP53在复杂核型、单体核型及-17/17p-的检出率分别为59.5%、38.1%、33.3%。亚组分析显示:TP53基因异常在AML和ALL复杂核型中的检出率分别为73.1%和40%,差异具有统计学意义。共发现TP53基因变异类型41种,且其中位变异频率为43.58%。75.6%变异位于DNA结合结构域。伴随变异基因主要为TET2、IKZF1。可评价疗效的18例AML和17例ALL患者,1疗程的完全缓解(complete remission,CR)率分别为22.2%和94.12%,差异有统计学意义。4例达CR的AML和16例达CR的ALL的中位RFS分别为174和246天,差异无统计学意义。AML和ALL的中位OS分别为20和375天,差异有统计学意义。结论TP53基因变异与AML复杂核型相关,而在ALL无显著影响。TP53基因变异位点主要分布于DNA结合结构域。伴TP53基因变异的AML缓解率低于ALL。伴TP53基因变异的AL患者,预后差,应尽可能早行异基因造血干细胞移植术,延长患者生存时间。Objective To explore the clinical characteristics and prognostic values ofTP53 gene variant in patients with acute leukemia(AL).Methods The clinical data of 44 newly diagnosed AL patients withTP53 variant detected by next-generation sequencing(NGS)were analyzed retrospectively.Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis,and conventional R-banding technique was used for karyotype analysis.The clinical features,cytogenetics,gene variant,curative effect and survival of AL patients withTP53 gene variant were analyzed.Results The median age of AML patients withTP53 gene variant(46 years)was higher than that of ALL patients(17.5 years),and the median number of bone marrow blasts(40.5%)was lower than the latter(89.2%),the differences were statistically significant(P<0.01).A total of 28 cases of abnormal karyotype were detected,of which 25 cases were complex karyotype,16 cases were monomeric karyotype,14 cases had-17/17p-.The detection rates ofTP53 in complex karyotype,monomeric karyotype and-17/17p-were 59.5%,38.1%and 33.3%,respectively.Subgroup analysis showed that the detection rate ofTP53 gene abnormalities in AML and ALL complex karyotypes was 73.1%and 40%respectively,the difference was statistically significant.A total of 41TP53 gene variant types were found,and the median variant frequency was 43.58%.75.6%variant was located in the DNA binding domain.The concomitant variant genes were mainly TET2 and IKZF1.Among 18 AML and 17 ALL patients who could be evaluated the curative effect,the CR rate of one course of treatment was 22.2%and 94.12%respectively,and the difference was statistically significant.The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively,the difference was statistically insignificant.The median OS of AML and ALL was 20 and 375 days respectively,the difference was statistically significant.Conclusion TheTP53 gene variant is associated with the complex karyotype of AML,but has no significant effect o

关 键 词：急性白血病 TP53基因 复杂核型 预后 

分 类 号：R733.71[医药卫生—肿瘤]