慢性髓细胞白血病患者骨髓单个核细胞miR-203、miR-451、miR-17表达及其临床意义  

Expression levels and clinical significance of miR-203,miR-451 and miR-17 in chronic myeloid leukemia

作　　者：杨再林[1,2] 叶枫[1] 但国蓉[1] 陈洁平[2] 张勇[2] 邹仲敏[1] 

机构地区：[1]第三军医大学军事预防医学院毒理研究所,重庆400038 [2]第三军医大学西南医院血液科,重庆400038

出　　处：《第三军医大学学报》2014年第22期2296-2300,共5页Journal of Third Military Medical University

基　　金：全军医学科技"十二五"重大项目(AWS11C004);国家自然科学基金面上项目(31171118)~~

摘　　要：目的分析探讨miR-203、miR-451、miR-17在慢性髓细胞白血病(chronic myeloid leukemia,CML)骨髓单个核细胞中表达水平的动态变化及在不同治疗方案后的表达差异,评价miR-203、miR-451、miR-17的表达水平在CML诊治中应用的可行性。方法收集2011年1月至2014年1月在西南医院经细胞形态学、免疫学、细胞遗传学及分子生物学(morphologie,immunophenotypie,cytogenetic,molecular,MICM)联合检测,由WHO造血组织和淋巴系统肿瘤分类的标准确诊为CML的患者98例及20例正常对照,采用实时定量PCR检测miR-203、miR-451、miR-17的表达水平,同步检测BCR-ABL融合基因的表达水平。结果 1 CML患者的miR-203表达水平明显低于对照组(P<0.05),且逐步多元回归分析显示miR-203与BCR-ABL融合基因表达水平呈负相关(r=-0.934,P<0.01);2 CML患者的miR-451表达水平明显低于对照组(P<0.05),miR-451与BCR-ABL融合基因表达水平呈负相关(r=-0.917,P<0.01);3 miR-17表达水平在CML-CP患者中上升,在CML-AP、BP患者中下调,差异有统计学意义(P<0.05);4 3种miRNA表达水平均提示传统化疗组与TKI治疗组、造血干细胞移植组有统计学差异,而TKI治疗组与造血干细胞移植组无统计学差异。结论 miR-203、miR-451、miR-17表达水平与BCR-ABL融合基因表达水平、CML疾病分期、治疗和预后评估等均有密切关系,有望成为CML新的生物学标志。Objective To investigate the dynamic expression levels of miR-203,miR-451 and miR-17 at different stages of chronic myeloid leukemia（ CML） and after different treatment regimens in order to assess the diagnostic,staging,treatment,and prognostic roles of these miRNAs as biomarkers in CML. Methods Totally 98 CML patients diagnosed according to MICM tests [bone marrow smear,biopsy,chromosome banding analysis,flow cytometry（ FCM）,and fluorescence in situ hybridization（ FISH）,namely MICM classification]and WHO criteria,and 20 healthy volunteers were recruited from Jan. 2011 to Jan. 2014 in the Southwest Hospital. Their marrow fluid were harvested and bone marrow mononuclear cells were isolated. Expression levels of miR-203,miR-451 and miR-17 were tested by real-time quantitative PCR,together with the expression of BCR-ABL fusion gene. Results Compared with normal controls,the expression levels of miR-203 was significantly down-regulated（ P〈0. 05）. Stepwise multiple regression analysis indicated that the expresssion of miR-203 was negatively correlated with that of BCR-ABL（ r =-0. 934,P 0. 01）. miR-451 level was obviously lower in CML patients than in controls（ P〈0. 05）,which was negatively correlated with BCR-ABL（ r =-0. 917,P 0. 01）. Expression of miR-17 was upregulated in chronic myelogenous leukemia-chronic phase（ CML-CP）,and downregulated in chronic myelogenous leukemia-advance phase（ CML-AP） and chronic myelogenous leukemia-blastic phase（ CML-BP）,all with significant differences（ P〈0. 05）. The expression levels of these 3 miRNAs were significantly different among traditional chemotherapy group,TKI group,and hematopoietic stem cell transplantation group, but there was no difference between the latter 2 groups.Conclusion As the expression levels of miR-203,miR-451 and miR-17 are highly correlated with the level of BCR-ABL fusion gene and the CML staging,treatment and prognosis,they might be regarded as novel biomarkers for CML.

关 键 词：miR-203 miR-451 miR-17 慢性髓细胞性白血 基因表达 

分 类 号：R394.3[医药卫生—医学遗传学] R730.43[医药卫生—基础医学]