急性淋巴细胞白血病儿童的分子生物学特点及预后分析  

Molecular Biological Characteristics and Prognosis of Children with Acute Lymphoblastic Leukemia

作　　者：密鑫 辛聪 潘俞夙 李艳 郭雷 王文鹏 高吉照 MI Xin;XIN Cong;PAN Yusu(Department of Pediatric Hematology and Oncology,Affiliated Hospital of Xuzhou Medical University,Jiangsu 221002,China)

机构地区：[1]徐州医科大学附属医院儿科血液与肿瘤病区,221002

出　　处：《医学研究杂志》2024年第11期144-149,共6页Journal of Medical Research

摘　　要：目的 分析急性淋巴细胞白血病(acute lymphoblastic leukemia, ALL)患儿的分子生物学特点,探讨其对预后的影响。方法 收集2017年1月~2021年2月徐州医科大学附属医院新发104例ALL患儿的临床资料,分析融合基因和突变基因的检出情况及对临床特点和预后的影响。结果 男性64例,女性40例;初诊中位年龄5岁(3个月~14岁);B-ALL 95例,T-ALL 9例;死亡13例,复发16例。104例患儿中,40例(38.5%)检测出9种融合基因,包括TEL-AML1、BCR-ABL1、MLL重排、E2A-PBX1、SIL-TAL1等,SIL-TAL1在T-ALL中发现,其余8种融合基因均在B-ALL中发现。行突变基因检测的96例患儿中,65例(67.7%)检测到33种突变基因,突变率较高为KRAS、NRAS、FLT3、IKZF1、TP53和PAX5等,B-ALL中突变率较高的基因为KRAS、NRAS,T-ALL中突变率较高的基因为NOTCH1、FBWX7。MLL重排组初诊年龄小,BCR-ABL1阳性组初诊年龄大;MLL重排、BCR-ABL1、NOTCH1突变、IKZF1突变阳性组初诊时易发生高白细胞血症,且BCR-ABL1和NOTCH1突变阳性组乳酸脱氢酶(lactate dehydrogenase, LDH)高;异常核型在BCR-ABL1、IKZF1突变阳性的患儿中更常见。伴MLL重排的患儿3年总生存(overall survival, OS)率及无事件生存(event-free survival, EFS)率低,BCR-ABL1阳性的患儿3年OS率低,IKZF1突变组的3年EFS率低。巩固治疗后,TEL-AML1未转阴与该亚型患儿复发有关(P<0.05)。结论 不同分子生物学异常对ALL患儿的临床特点和预后的影响不同。Objective To analyze the molecular biological characteristics of children with acute lymphoblastic leukemia(ALL)and explore its influence on prognosis.Methods Clinical data of 104 newly diagnosed children with ALL in the Affiliated Hospital of Xuzhou Medical University from January 2017 to February 2021 were collected to analyze the detection of fusion genes and mutated genes and their effects on clinical characteristics and prognosis.Results There were 64males and 40 females.The median age at first visit was 5 years(3months to 14 years);B-ALL 95 cases,T-ALL 9 cases;there were 13deaths and 16 relapses.Among the 104 children,40 cases(38.5%)were detected with 9 fusion genes,including TEL-AML1,BCR-ABL1,MLL rearrangement,E2A-PBX1,SIL-TAL1,etc.SIL-TAL1 was found in T-ALL,and the other 8 fusion genes were found in B-ALL.Of the 96 children who underwent mutated gene detection,65 cases(67.7%)detected 33mutated genes,the high mutation rate was KRAS,NRAS,FLT3,IKZF1,TP53 and PAX5,and the high mutation rate was KRAS and NRAS in B-ALL.The high mutation rates of T-ALL were NOTCH1 and FBWX7.The age of first diagnosis was younger in the MLL rearrangement group and older in the BCR-ABL1 positive group.MLL rearrangement,BCR-ABL1,NOTCH1mutation,IKZF1mutation positive group was prone to hyperleukaemia at first diagnosis,and BCR-ABL1 and NOTCH1mutation positive group had high lactate dehydrogenase(LDH).Abnormal karyotypes were more common in children with positive BCR-ABL1 and IKZF1mutations.The 3-year overall survival(OS)rate and event-free survival(EFS)rate were low in children with MLL rearrangement,the 3-year OS rate was low in children with BCR-ABL1 positive,and the 3-year EFS rate was low in the IKZF1mutant group.The failure of TEL-AML1 to turn negative after consolidation therapy was associated with recurrence in children with this subtype(P<0.05).Conclusion Different molecular biological abnormalities have different effects on the clinical characteristics and prognosis of children with ALL.

关 键 词：急性淋巴细胞白血病 融合基因 突变基因 预后 

分 类 号：R72[医药卫生—儿科]