儿童急性粒细胞白血病及其亚型的微小RNA表达  

microRNA expression in childhood acute granulocytic leukemia and its subtypes

作　　者：罗学群[1] 徐令[2] 柯志勇[1] 黄礼彬[1] 张晓莉[1] 张丽丹[1] 

机构地区：[1]中山大学附属第一医院儿科,广州510080 [2]中山大学附属第二医院医学研究中心

出　　处：《中华肿瘤杂志》2011年第11期831-835,共5页Chinese Journal of Oncology

基　　金：国家自然科学基金（30672254）

摘　　要：目的分析儿童急性白血病（AL）的微小RNA（miRNA）表达谱，深化对AL的分型诊断乃至发病机制和预后的认识。方法应用基因芯片技术分析93例AL患儿骨髓的miRNA表达谱，另选12例儿童特发性血小板减少性紫癜作为对照，应用实时定量聚合酶链反应（PCR）方法印证miRNA的异常表达。结果粒细胞系的急性髓细胞白血病（AML）与急性淋巴细胞白血病的miRNA表达谱明显不同，前者分别有17种和18种miRNA明显表达上调和下调，后者分别有21种和11种表达上调和下调。根据法、美、英协作组（FAB）形态学分型标准，在粒系AML的M1、M2和M3亚型中，miRNA表达各异，分别有miR-335、miR-126和miR-125b特异性高表达，基因芯片能区分这3种亚型。在M2和M3亚型中，AML1-ETO阳性组和PML—RARer阳性组的miR-126和miR-125b表达水平，分别比阴性组明显升高（均P〈0．01）。miR-335和miR-146在粒系AML表达上调，不同于在成人患者中研究报道的结果。结论miRNA可能为AL的分类和诊断提供新的生物学标记。各型AL之间有不同的miRNA调控网络，可能存在与特异的miRNA表达相关的不同发病机制和预后。Objective Recent studies have suggested that there is a close relation between microRNA and acute leukemia （AL）. The aim of this study was to investigate and better understand the classification and diagnosis of AL as well as pathogenesis and prognosis of this disease. Methods A total of 93 children with AL and and 12 cases of idiopathic thrombocytopenic purpura （as control group） were enrolled in this study. Mieroarray chip analysis of their bone marrow samples was conducted to evaluate the microRNA profiles. Quantitative real-time PCR was performed for validating the abnormal expression of microRNA. Results The microRNA expression profiles were different between acute granulocytic leukemia and acute lymphoblastic leukemia and also between the three subtypes （M1, M2 and M3 ） of acute granulocytic leukemia according to FAB classification based on leukemic cell differentiation. These three subtypes of leukemia could be identified by unsupervised hierarchical cluster analysis of microRNA expression and had specific up-regulation of miR-335, miR-126 and miR-125b, respectively. However, in the M2 and M3 subtypes with positive AML1-ETO and PML-RARα, respectively, which have a better prognosis, the expressions of miR-126 and miR-i25b were significantly higher than those with negative AML1-ETO and PML-RARα. Further more, miR-335 and miR-146 were up-regulated in acute granulocytic leukemia observed in this study, which are different from those reported for adult patients. Condusions microRNA cascade may serve as new biomarkers for the classification and diagnosis of pediatric AL. It is also suggested that there might be different pathogenesis and prognosis between AL types related to specific expression and regulation of microRNA.

关 键 词：白血病 髓样 微小RNA 儿童 

分 类 号：R733.71[医药卫生—肿瘤]