儿童急性淋巴细胞白血病融合基因动态检测及意义

DYNAMIC TESTING OF FUSION GENES IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA AND ITS SIGNIFICANCE

目的探讨在儿童急性淋巴细胞白血病(ALL)治疗过程中融合基因动态检测的临床意义。方法ALL病儿168例,融合基因阴性84例,融合基因阳性84例,其中包括TEL-AML1阳性26例、EVI1阳性22例、其他融合基因阳性24例、双融合基因阳性12例。在治疗前及治疗过程中采用基因扩增技术检测融合基因的表达,分析融合基因表达与ALL预后的关系;对于融合基因阳性且未持续转阴初发ALL病儿,应用COX比例风险回归模型分析影响预后的危险因素。结果 ALL病儿融合基因阳性对总生存(OS)率无显著影响(P>0.05),对无事件生存(EFS)率有显著影响(χ~2=14.615,P<0.05);TEL-AML1阳性病儿EFS率较融合基因阴性病儿、其他融合基因阳性病儿显著升高(χ~2=6.877、3.926,P<0.05)。TEL-AML1、其他融合基因持续转阴病儿3年EFS率较相应融合基因未持续转阴病儿显著升高(χ~2=8.925、6.091,P<0.05),EVI1、双融合基因持续转阴病儿3年EFS率与相应融合基因未持续转阴病儿比较差异无显著性(P>0.05)。融合基因1年内是否转阴对病儿3年EFS率无明显影响(P>0.05)。年龄>10岁,免疫分型为T细胞型,临床危险度为高危,诱导缓解治疗第15、33天微小残留病≥10-2的融合基因阳性且未持续转阴初发ALL病儿3年EFS率显著降低,差异有统计学意义(χ~2=4.542~7.974,P<0.05)。融合基因阳性且未持续转阴初发ALL病儿,年龄>10岁(95%CI=2.063~25.901,P<0.05)、免疫分型为T细胞型(95%CI=1.009~22.084,P<0.05)是影响预后的危险因素。结论融合基因动态检测对于判断ALL病儿预后有重要意义,有助于指导个体化治疗。

Objective To investigate the dynamic testing of fusion genes in the treatment of childhood acute lymphoblas- tic leukemia （ALL） and its clinical significance. Methods A total of 168 children with ALl. were enrolled in this study, inclu- ding 84 fusion gene-negative children and 84 fusion gene positive children, which consisted of 26 TEL-AML 1 positive children, 22 EVil-positive children, 24 other fusion gene-positive children, and 12 dual fusion gene positive children. Gene amplification was used to detect the fusion gene expression before and after treatment to analyze the relationship between the fusion gene expression and the prognosis of ALL. The prognostic factors for ALL were analyzed by Cox proportional hazards regression model in fusion gene-positive incipient ALL children without sustained clearance. Results Being positive for fusion gene had no significant effect on overall survival （OS） rate （P〉0.05） and had a significant effect on event free survival （EFS） rate in ALL children （Z2 = 14.615,P 〈0.05）. The TEL-AML 1-positive ALL children had a significantly higher EFS rate than the fusion gene negative Aid. children and the other fusion gene positive ALL children （χ2 =6.877,3.926% P〈0.05）. The ALL children with the sustained clea rance of TEL-AML 1 and other fusion genes had significantly higher 3-year EFS rates than the ALL children without the sustained clearance of TEL-AML1 and other fusion genes （χ2=8.925,6.091;P〈0.05）. However, there was no significant difference in 3- year EFS rate between the ALl. children with and without the sustained clearance of EVIl and dual fusion gene （P〉0.05）. The clearance of fusion gene within the first year had no significant effect on 3 year EFS rate in ALL children （P〉0.05）. The following factors could significantly decrease the 3-year EFS rate in the fusion gene-positive incipient ALL children without sustained clearance： age over 10 years, T-cell Aid., high-risk ALL, and minimal residual disease （MRD） ≥10 2 on the 15th and 33th days of remission induction therapy （χ2 =4.542--7.974, P 〈0.05）. Multivariate analysis suggested that the prognostic factors were age over 10 years （95%CI=2.063--25.901,P〈0.05） and T-cell ALL （95%CI=1.009--22.084,P〈0.05） in the fusion gene-positive incipient ALL children without sustained clearance. Conclusion Dynamic testing of fusion genes is of great prognostic signifi- cance and is helpful for the individualized treatment of ALL patients.