EVI1基因阳性的儿童急性髓细胞性白血病生物学及临床特征分析

目的 研究EVI1 基因在急性髓细胞性白血病（AML）患儿中的表达及EVI1 基因阳性AML 患儿的临床特征。方法 收集分析EVI1 阳性患儿的临床资料；采用RT-PCR 法和实时荧光定量聚合酶链反应法（RQ-PCR）定性和定量测定EVI1 的表达；流式细胞术检测骨髓细胞免疫表型；多参数流式细胞术（MFC）监测微小残留白血病（MRD）；同时对染色体进行检查。结果 241 例AML 患儿中，有33 例EVI1 基因表达呈阳性（13.7%）；与EVI1 基因表达阴性的AML 患儿相比，EVI1 阳性AML 患儿的初诊年龄、外周血白细胞计数、血红蛋白含量和血小板计数差异均无统计学意义（均P>0.05），但女性患儿比例增加（P<0.05）；EVI1 表达改变与临床缓解和MRD 改变不同步，部分患儿EVI1 转阴滞后于临床缓解和MRD 转阴，而部分患儿临床未缓解或MRD 仍呈阳性，但EVI1 已转阴；EVI1 常与其他融合基因共表达；免疫表型分析提示EVI1 阳性AML 患儿高表达CD33（100%）、CD38（88%）和HLADR（76%）；15 例患儿发现染色体结构或数目异常；EVI1 表达阳性AML 患儿第1 疗程完全缓解（CR）率明显低于EVI1 表达阴性患儿（P<0.05）。结论 EVI1 基因表达阳性的AML 患儿近期预后差；EVI1 基因在AML 的病程中活化不是孤立的，而是与其他基因相互作用或染色体异常的结果，其活化机制及功能还需进一步研究。

Clinical and biological characteristics of childhood acute myeloid leukemia with EVI1 gene positive expression

Objective To study the expression of ecotropic viral integration site (EVI1) gene in childhood acute myeloid leukemia (AML) and the clinical features of EVI1-positive children with AML. Methods The clinical data of EVI1-positive children with AML were collected and analyzed. RT-PCR and real-time quantitative PCR were used for qualitative and quantitative analysis of expression of EVI1. Flow cytometry (FCM) was used for determining the immunophenotypes of bone marrow cells. Multiparameter FCM was used for monitoring minimal residual disease. The karyotypes were determined. Results Of 241 children with AML, 33 (13.7%) were positive for EVI1 expression. There were no significant differences in age at first visit as well as the white blood cell count, hemoglobin level, and platelet count in peripheral blood between EVI1-positive and EVI1-negative children with AML (P>0.05), but EVI1-positive children had a significantly increased proportion of females compared with EVI1-negative children (P<0.05). The change in EVI1 expression was not synchronous with clinical remission and the change of MRD: some children had clinical remission or negative conversion of MRD before negative conversion of EVI1, while some had negative conversion of EVI1 before clinical remission or while MRD showed positive. EVI1 gene was usually co-expressed with other fusion genes. CD33 (100%), CD38 (88%), and HLADR (76%) were highly expressed in EVI1-positive children with AML. Abnormal chromosome structure or number was found in 15 patients. Compared with EVI1-negative children, EVI1-positive children had significantly lower complete remission rates after the first course of treatment (P<0.05). Conclusions EVI1-positive children with AML have a poor short-term prognosis. In the development of AML, the activation of EVI1 gene is not isolated, but the result of interactions with other genes or chromosome abnormalities, and the mechanism of activation and its function need further study.