ZNF384融合儿童B系急性淋巴白血病的临床及分子特征  

Clinical and molecular characteristics of ZNF384 fusion positive B-cell acute lymphoblastic leukemia in children

作　　者：张伟娜 王鹏飞 朱璐 胡政斌 丁文姣 王嘉怡 何映谊 ZHANG Weina;WANG Pengfei;ZHU Lu;HU Zhengbin;DING Wenjiao;WANG Jiayi;HE Yingyi(Department of Hematology,Guangzhou Women and Children′s Medical Center,Guangzhou 510623,China)

机构地区：[1]广州市妇女儿童医疗中心血液肿瘤科,广州510623

出　　处：《中国小儿血液与肿瘤杂志》2022年第4期242-248,共7页Journal of China Pediatric Blood and Cancer

基　　金：广州市妇女儿童医疗中心临床博士启动科研基金(5001-1600004)。

摘　　要：目的总结我中心ZNF384融合阳性儿童B系急性淋巴细胞白血病(B-ALL)的临床及实验室特点,为该亚组白血病的诊断及治疗提供依据。方法收集2018年4月—2021年12月期间我院ZNF384相关融合阳性的B-ALL患儿的临床资料,分析该亚组白血病患儿的临床特点、实验室特征以及治疗效果。结果通过血液肿瘤全景式基因变异分析,在420例初发B-ALL和25例复发B-ALL中共发现15例ZNF384融合阳性病例,其中13例为初发,占比为3.1%(13/420);2例为复发,占比8.0%(2/25)。在融合伙伴方面,TCF3最常见,共6例,另有5例EP300-ZNF384,2例CREBBP-ZNF384,1例ARID1B-ZNF384,1例未报道过的DDX3X-ZNF384。6例TCF3-ZNF384融合患儿年龄相对较小。ZNF384融合的白血病细胞免疫表型为pro-B或common-B,CD10不表达或低度表达,多伴髓系抗原CD33、CD13表达。ZNF384融合伴随多种基因突变,12例患者(80%)存在激酶信号通路相关基因突变,最常见为NRAS突变。13例初发ALL患者分别采取中国儿童癌症协作组(CCCG)-ALL 2015或2020化疗方案,均能获得完全缓解。1例TCF3-ZNF384阳性婴儿白血病患儿在化疗维持阶段后期微小残留病灶转为阳性。2例复发病例按CCCG复发ALL2017方案化疗,能再次获得缓解,其中1例为早期复发并伴TCF3-ZNF384融合。结论ZNF384融合在儿童B-ALL中常见,有多个伙伴基因,具有独特的免疫表型,伴随激酶信号通路突变,整体预后良好。TCF3-ZNF384融合患儿年龄相对较小,可能相对预后不良。新发现的DDX3X-ZNF384融合进一步丰富了对ZNF384融合的认识。Objective To summarize the clinical and laboratory characteristics of ZNF384 fusion positive B-cell acute lymphocytic leukemia(B-ALL)in our center,so as to provide basis for the diagnosis and treatment of this B-ALL subtype.Methods Clinical data of ZNF384 fusion positive B-ALL children in our hospital from April 2018 to December 2021 were collected,the clinical characteristics,laboratory characteristics and prognosis of these children were analyzed.Results After panoramic gene variation analysis of hematologic malignancies,a total of 15 ZNF384 fusion positive cases were found in 420 primary and 25 relapsed B-ALL patients,including 13 primary B-ALL patients(3.1%;13/420)and two relapsed cases(8.0%;2/25).Among the 15 cases,six had TCF3-ZNF384,five had EP300-ZNF384,two had CREBBP-ZNF384,one had ARID1B-ZNF384,and one had the newly found DDX3X-ZNF384 fusion.The 6 patients with TCF3-ZNF384 fusion were relatively young.The immunophenotype of the leukemia cells with ZNF384 fusion was pro-B or common-B,with little or low expression of CD10,accompanied by CD13 and CD33 expression.ZNF384 fusion was coexisted with a variety of gene mutations,with kinase signaling pathway-related gene mutations in 12 cases(80%)and the most common NRAS mutations.The 13 primary B-ALL patients received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 or 2020 chemotherapy,respectively,and all achieved complete remission.The minimal residual disease of the TCF3-ZNF384 positive infant case turns positive during the late maintenance phase of chemotherapy.Two relapsed patients were able to achieve complete remission with CCCG Relapsed ALL 2017 regimen,with one case early relapse and carrying TCF3-ZNF384 fusion.Conclusions ZNF384 fusion is common in children with B-ALL,with multiple fusion partners.This subtype of B-ALL has a unique immunophenotype,accompanies with kinase signaling pathway mutations,and shows a good therapeutic effect with current treatment options.TCF3-ZNF384 positive cases with younger age may have a relatively poor prog

关 键 词：B系急性淋巴细胞白血病 ZNF384融合 DDX3X-ZNF384 

分 类 号：R733.71[医药卫生—肿瘤]