摘要
目的探讨儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)融合基因表达情况及临床特点。方法回顾性分析2018年1月至2021年12月河南省儿童医院收治的341例初发ALL患儿的临床资料,根据融合基因检出情况分为融合基因阳性组和阴性组,比较不同组间的临床特点、完全缓解率、复发率、死亡率等指标。结果341例ALL患儿融合基因阳性检出率为48.1%(164/341),共检出15种融合基因,包括TEL-AML1、KMT2A重排、E2A-PBX1、BCR-ABL1、MEF2D重排、SIL-TAL1等。不同年龄组间融合基因表达差异有统计学意义(P<0.001),其中KMT2A重排多见于<1岁组,MEF2D重排多见于>10岁组。KMT2A重排+、BCR-ABL1+、MEF2D重排+和SIL-TAL1+患儿易发生高白细胞血症,且后3类患儿更易发生中枢神经系统受累。KMT2A重排(P<0.001)、BCR-ABL1(P=0.001)、MEF2D重排(P=0.001)多见于高危患者。融合基因阳性组基因突变检出率显著低于阴性组(27.9%vs 53.6%,P<0.001)。Ph-like基因仅在急性B淋巴细胞白血病患儿中检出,且以IK6亚型检出率最高,其中40%(8/20)的IK6亚型与BCR-ABL1关联。在治疗第33天和第12周评估中,BCR-ABL1+ALL患儿通过聚合酶链式反应检测的微小残留病(minimal residual desease,MRD)完全缓解率均低于对应时间点通过流式细胞术检测的MRD完全缓解率(均P<0.05)。融合基因阳性组复发率明显高于阴性组(P<0.001),但两组死亡率差异无统计学意义(P=0.080),其中KMT2A重排+患者复发率及死亡率均最高。结论初发ALL患儿因融合基因表达不同其临床特点、治疗缓解率、复发率和死亡率存在显著差异,治疗过程中监测MRD是评估危险度分层、判断预后的重要依据。
Objective To investigate the expression of fusion genes and clinical characteristics in children with acute lymphoblastic leukemia(ALL).Methods The clinical data of 341 newly diagnosed ALL children patients admitted to Henan Children's Hospital from January 2018 to December 2021 were enrolled and retrospectively analyzed.The patients were divided into positive group and negative group according to the detection of fusion genes,and the clinical characteristics,complete response rate,recurrence rate and mortality as well as other indicators were compared among different groups.Results The positive detection rate of fusion genes in 341 children with ALL was 48.1%(164/341),with a total of 15 fusion genes were detected,including TEL⁃AML1,KMT2A rearrangement,E2A⁃PBX1,BCR⁃ABL1,MEF2D rearrangement,SIL⁃TAL1,etc.There was a statistically significant difference in fusion gene expression among different age groups(P<0.001),with KMT2A rearrangement and MEF2D rearrangement more common in the<1 years old group and the>10 years old group,respectively.Hyperleukopenia was more common in children with KMT2A rearrangement+,BCR⁃ABL1+,MEF2D rearrangement+and SIL⁃TAL1+,and the children patients with latter three types were more prone to central nervous system involvement.KMT2A rearrangement(P<0.001),BCR⁃ABL1(P=0.001),and MEF2D rearrangement(P=0.001)were more common in the high⁃risk patients.The detection rate of gene mutation in the fusion gene positive group was significantly lower than that in the negative group(27.9%vs 53.6%,P<0.001).The Ph⁃like gene was only detected in children with acute B⁃lymphocytic leukemia,and the highest detection rate was found in the IK6 subtype,with 40%(8/20)of the IK6 subtype associated with BCR⁃ABL1.In the evaluation on the 33rd day and the 12th week of treatment,the complete remission rate of minimal residual desease(MRD)detected by polymerase chain reaction in BCR⁃ABL1+ALL patients was lower than that of MRD detected by flow cytometry at the corresponding time point(P<0.05).The
作者
李宁
丁璐月
刘炜
王天有
LI Ning;DING Luyue;LIU Wei;WANG Tianyou(Hematology and Oncology Department,Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital/Zhengzhou Children's Hospital,Zhengzhou 450000,China;Hematology Oncology Center,Beijing Children's Hospital,Capital Medical University,Beijing 100045,China)
出处
《中国癌症防治杂志》
CAS
2023年第3期311-316,共6页
CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT
基金
河南省科技发展计划项目(222102310616)。
关键词
急性淋巴细胞白血病
儿童
融合基因
治疗反应
预后
Acute lymphoblastic leukemia
Children
Fusion gene
Therapeutic response
Prognosis
