儿童急性淋巴细胞白血病染色体及融合基因表达的临床研究

目的 研究儿童急性淋巴细胞白血病(ALL)细胞遗传学改变和预后的关系.方法 采用反转录聚合酶链反应(RT-PCR)法检测103例儿童ALL患者常见的融合基因、染色体数和结构,分析染色体和融合基因的变化对治疗反应及生存时间的影响.结果 103例患儿中,52例染色体数正常,未检出融合基因.51例检出融合基因,其中TEL-AML1阳性22例,bcr-abl阳性10例,E2A-PBX1阳性11例,MLL-AF4阳性2例,HOX11阳性3例,SIL-TAL1 1例,dupMLL 1例,TLS-ERG 1例.bcr-abl组平均生存时间短于未检出异常基因组、TEL-AML1组、E2A-PBX1组,差异均有统计学意义[(16.5±3.8)个月比(34.6±1.7)个月、(31.6±1.4)个月、(34.5±3.3)个月,均P＜0.05],与其他异常基因组[(12.8±1.5)个月]差异无统计学意义(P＞0.05).未检出异常基因组平均生存时间与TEL-AML1组及E2A-PBX1组比较,差异均无统计学意义(均P＞ 0.05),与其他异常基因组间差异有统计学意义(P＜0.05).染色体数异常18例,其中亚二倍体4例,超二倍体14例.亚二倍体患儿平均生存时间短于超二倍体患儿[(19.8±4.8)个月比(37.5±2.2)个月,x 2=7.375,P=0.007],易复发.初诊时不同白细胞计数和乳酸脱氢酶水平的患儿平均生存时间差异有统计学意义(均P＜ 0.05).结论 融合基因及染色体数等细胞遗传学指标的检测可用于判断儿童ALL的预后和转归,对实现个体化治疗有重要指导意义.

Chromosomal alteration and fusion gene expression in children with acute lymphoblastic leukemia: a clinical study

Objective To study the relationship between the cytogenetic and the prognosis in children with acute lymphoblastic leukemia (ALL).Methods RT-PCR was used to detect the common fusion gene,chromosome number and structure in 103 children with ALL.The effects of chromosome and fusion gene changes on treatment response and survival time were analyzed.Resuts Among 103 children with ALL,52 cases had normal gene number and no fusion gene,and 51 cases had fusion gene,including 22 cases with TEL-AML1 positive,10 cases with bcr-abl positive,11 cases with E2A-PBX1 positive,2 cases with MLL-AF4 positive,3 cases with HOX11 positive,1 case with SIL-TAL1,1 case with dupMLL and 1 case with TLS-ERG.The average survival time of bcr-abl group was shorter than that of non-fusion gene group,TEL-AML1 group and E2A/PBX1 group respectively,and there were significant differences [(16.5±3.8) months vs (34.6±1.7) months,(31.6±1.4) months,(34.5±3.3) months,all P ＜ 0.05],but there was no significant difference between bcr-abl group and other fusion gene group [(12.8±1.5) months,P ＞0.05].The average survival time of non-fusion gene group had no significant differences compared with TEL-AML1 group and E2A-PBX1 group(both P ＞ 0.05),but had significant differences with other fusion gene group (P ＜ 0.05).There were 18 patients with abnormal chromosome number and structure,including 4 cases with diploid,14 cases with super diploid.The patients with diploid had shorter survival time [(19.8±4.8) months vs (37.5 ±2.2) months,x2 =7.375,P =0.007] and were easier to relapse than ones with super diploid.The average survival time of patients with different white blood cell count and lactate dehydrogenase levels had significant differences (both P ＜ 0.05).Conclusion Detection of cytogenetics and chromosome fusion genes can be used to determine the prognosis and outcome of children with ALL,which has important guiding significance for the realization of individualized treatment.