E-cadherin基因在儿童急性白血病中的表达及其临床意义  

E-cadherin Expression in Children with Acute Leukemia and Its Clinical Significance

作　　者：包斌霞 安曦洲 李朋飞[1] 李永婧 崔颖慧[1] 唐雪[1] 刘奇慧[1] 胡艳妮[1] 刘威 梁绍燕 于洁[1] BAO Bin-Xia;AN Xi-Zhou;LI Peng-Fei;LI Yong-Jing;CUI Ying-Hui;TANG Xue;LIU Qi-Hui;HU Yan-Ni;LIU Wei;LIANG Shao-Yan;YU Jie(Department of Hematology & Oncology,Childhren's Hospital Affiliated to Chongqing Medical University,Key Laboratory of Child Development and Disorders of Ministry of Education,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院血液肿瘤科儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地儿科学重庆市重点实验室,重庆400014

出　　处：《中国实验血液学杂志》2019年第2期339-347,共9页Journal of Experimental Hematology

基　　金：国家自然科学基金委青年科学基金项目(81700158)

摘　　要：目的:研究E-cadherin基因在儿童急性白血病(AL)中的表达及其与临床指标的相关性,并探讨其可能的调控机制。方法:采用实时荧光定量PCR检测135例初诊AL患儿骨髓单个核细胞中E-cadherin mRNA的表达水平,并分析其表达水平与临床指标的相关性;应用Western blot法检测E-cadherin、β-catenin、Akt、p-Akt信号通路相关蛋白的表达;同时收集22例非恶性血液病患儿的骨髓作为对照。结果:B-ALL、T-ALL、AML组中E-cadherin mRNA的表达均低于对照组(P<0.01)。在B-ALL中,中危组患儿E-cadherin基因表达水平较标危组显著下降(P<0.05);伴有脾脏浸润的患儿E-cadherin基因表达水平亦显著降低(P<0.01);而在T-ALL、AML患儿各临床指标分组中,E-cadherin基因表达水平均无显著差异。在B-ALL患儿中,免疫分型为Common-BALL的患儿E-cadherin基因表达水平较其他B-ALL患儿显著升高(P<0.01)。而在3种AL的FAB分组间均未见E-cadherin表达差异。基于计量资料的相关性分析表明,B-ALL患儿中,随着E-cadherin表达水平的下调,初诊外周血白细胞(WBC)计数、乳酸脱氢酶(LDH)水平有升高趋势(r=-0.419,r=-0.269),而初诊外周血血小板水平呈下降趋势(r=0.335);在T-ALL患儿中,E-cadherin表达水平与LDH、初诊骨髓幼稚细胞比例呈显著负相关(r=-0.567,r=-0.557);而在AML患儿中,随着E-cadherin表达水平下调,初诊WBC计数水平和初诊骨髓幼稚细胞比例呈上升趋势(r=-0.368,r=-0.391)。与对照组比较,3种AL患儿中E-cadherin表达水平下调(P<0.001),而β-catenin、Akt则上调(P<0.01),p-Akt、p-Akt/Akt表达量在T-ALL中上调(P<0.01)。结论:E-cadherin基因表达降低或缺失是儿童急性白血病的预后不良相关因素,可能通过激活Wnt/β-catenin和PI3K/Akt信号通路,促进肿瘤的发生,并引起细胞的一系列恶性生物学行为,E-cadherin有望成为判断预后和指导个性化治疗的指标。Objective:To investigate the correlation of E-cadherin expression level with the clinical characterastics in children with acute leukemia(AL),and to explore the possible regulatory mechanism.Methods:Real-time quantitative RT-PCR was applied to detect the expression level of E-cadherin in bone marrow samples from 135 child patients diagnosed as AL,and its relevance with clinical indicators was statistically analyzed.The expression levels of E-cadherin,β-catenin,and Akt/p-Akt were detected by using Western blot.The bone marrow samples from 22 children with nonmalignant hematological diseases were used as controls.Results:The expression level of E-cadherin significantly decreased in newly diagnosed patients with all 3 types of AL as compared with bone marrow samples from control group(P<0.01).In B-ALL group,compared with standard risk group,E-cadherin expression level significantly decreased in intermediate risk group(P<0.05).Moreover,the expression level of E-cadherin mRNA was also reduced in splenomegaly group(P<0.01).However,the correlation of E-cadherin level with clinical characteristics was not found in T-ALL and AML(P>0.05).The expression level of E-cadherin in the patients from Common-B-ALL group was higher than B-ALL patients with other immunophenotypes(P<0.01),while no significant difference was found among patients grouped by FAB classification.By the correlation analysis of measured data,lower E-cadherin expression level was found to be related with high WBC count and serum lactic dehydrogenase level(LDH)(r=-0.419,r=-0.269),but with low blood platelet count in B-ALL(r= 0.335).In T-ALL,expression of E-cadherin was found to be negatively correlated with LDH and percentage of immature cells in the bone marrow(r =-0.567,r =-0.557).In addition,the lower expression of E-cadherin was also found to be related with WBC count and percentage of immature cells in the bone marrow in newly diagnosed AML patients(r=-0.368,r=-0.391).Compared with control group,the expression of E-cadherin was down-regulated significant

关 键 词：E-CADHERIN基因 儿童急性白血病 危险因素 疾病预后 信号通路 

分 类 号：R733.71[医药卫生—肿瘤]