伴TP53突变的儿童B细胞急性淋巴细胞白血病9例临床分析  

Clinical analysis of 9 cases of childhood B-cell acute lymphoblastic leukemia with TP53 mutations

作　　者：林丹娜[1] 张晶鑫 资娟 张亚芥 张文鑫 黄子涵 夏霞宇 杨丽华[1] LIN Danna;ZHANG Jingxin;ZI Juan;ZHANG Yajie;ZHANG Wenxin;HUANG Zihan;XIA Xiayu;YANG Lihua(Department of Pediatric Hematology,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China;Laboratory of Molecular Diagnostics,Beijing GoBroad Boren Hospital,Beijing 100070,China)

机构地区：[1]南方医科大学珠江医院小儿血液科,广州510280 [2]高博博仁医院分子实验室,北京100070

出　　处：《中国小儿血液与肿瘤杂志》2024年第6期418-423,共6页Journal of China Pediatric Blood and Cancer

摘　　要：目的研究儿童B细胞急性淋巴细胞白血病(B-ALL)中TP53突变的发生情况及其临床特征。方法初诊儿童B-ALL患者194例,描述其TP53基因的突变情况,回顾分析其中伴TP53突变患儿的临床特征和治疗结果。结果194例初诊B-ALL患者中9例存在TP53突变,伴和不伴TP53突变患儿中位年龄分别为8(4~17)岁和4(0.5~15)岁(P=0.004);男女比例分别为9:0和116:78(P=0.012);常见分子遗传学异常的发生率没有统计学差异;低亚二倍体分型的发生率有统计学差异(P=0.002)。伴和不伴TP53突变患儿化疗后第15、33天及巩固化疗前骨髓流式细胞学微小残留病灶(MRD)转阴率无统计学差异。9例TP53突变的患儿,除1例缓解后放弃治疗并失访外,8例随访至今均无病生存。伴TP53突变的患儿中1例经1疗程化疗诱导缓解失败,1例巩固治疗前流式MRD未转阴,该2例患者均为TP53体系突变,且突变频率大于30%。5例TP53体系突变患者进行了TP53的定量监测,其中1例在流式MRD转阴后TP53定量仍持续升高。结论该儿童B-ALL队列中TP53突变发生率约4.6%,男性占优势,年龄较大,起病合并低亚二倍体,早期治疗反应与不伴TP53突变的患儿无差异;TP53突变频率用于白血病MRD监测存在局限性。Objective This study aimed to assess the prevalence of TP53 mutations in pediatric patients with B-cell acute lymphoblastic leukemia(B-ALL)and investigate the corresponding clinical features.Methods A retrospective analysis was conducted on 194 newly diagnosed cases of B-ALL.The occurrence of TP53 mutations was delineated,and clinical characteristics and treatment outcomes were examined in the subset with TP53 mutations.Results Among the 194 pediatric B-ALL cases,9 exhibited TP53 mutations.Patients with TP53 mutations had a median age of 8(4-17)years,whereas those without mutations had a median age of 4(0.5-15)years(P=0.004).Male-to-female ratios were 9:0 and 116:78,respectively(P=0.012).No significant differences were observed in the occurrence rates of frequently occurring molecular anomalies between patients with and without TP53 mutations.However,there was a statistically significant difference in the incidence of the low hypodiploid subtype(P=0.002).Conversion rates of minimal residual disease(MRD)assessed by flow cytometry on days 15 and 33 of chemotherapy and before consolidation therapy showed no statistical differences between patients with and without TP53 mutations.Among patients with TP53 mutations,one failed to achieve remission after one course of chemotherapy,and another did not attain MRD negativity before consolidation therapy.Both cases harbored TP53 somatic mutations with mutation frequencies exceeding 30%.With the exception of one patient who discontinued treatment after achieving remission and was lost to follow-up,the remaining 8 patients have maintained disease-free survival to date.Among the 5 patients with TP53 somatic mutations who underwent quantitative monitoring of TP53,one continued to exhibit an increase in TP53 levels after achieving MRD negativity.Conclusions The incidence of TP53 mutations in this pediatric B-ALL cohort was 4.6%.Clinical characteristics included a male predominance,older age,and a potential association with the low hypodiploid subtype.Early treatment response did

关 键 词：TP53突变 儿童B细胞急性淋巴细胞白血病 低亚二倍体 突变频率 

分 类 号：R73[医药卫生—肿瘤]