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.
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,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Apr;27(2):339-347. doi: 10.19746/j.cnki.issn.1009-2137.2019.02.005.
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.
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 non-malignant hematological diseases were used as controls.
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 significantly (P<0.01), while β-catenin, Akt significantly was up-regulated in 3 types of AL patients (P<0.01). The expression of p-Akt and p-Akt/Akt was up-regulated significantly in T-ALL (P<0.01).
Lower expression of E-cadherin is related factor of unfavourable prognosis in children with acute leukemia. The expression deficiency or down-regulation of E-cadherin may activate Wnt/β-catenin and PI3K/ Akt signaling pathways to promote the genesis and progress of haematological malignancies, thus resulting in a series of malignant biological behaviors in cells. E-cadherin may be a new prognostic indicator for pediatric acute leukemia, thus to guide individualized hemotherapy.
探讨E-钙黏蛋白表达水平与儿童急性白血病（AL）临床特征的相关性，并探索其可能的调控机制。
应用实时定量逆转录聚合酶链反应（RT-PCR）检测135例确诊为AL的儿童患者骨髓样本中E-钙黏蛋白的表达水平，并对其与临床指标的相关性进行统计学分析。采用蛋白质免疫印迹法检测E-钙黏蛋白、β-连环蛋白及Akt/p-Akt的表达水平。选取22例非恶性血液病患儿的骨髓样本作为对照。
与对照组骨髓样本相比，所有3种类型的初诊AL患者中E-钙黏蛋白表达水平均显著降低（P<0.01）。在B淋巴细胞白血病（B-ALL）组中，与标危组相比，中危组E-钙黏蛋白表达水平显著降低（P<0.05）。此外，脾肿大组E-钙黏蛋白mRNA表达水平也降低（P<0.01）。然而，在T淋巴细胞白血病（T-ALL）和急性髓系白血病（AML）中未发现E-钙黏蛋白水平与临床特征的相关性（P>0.05）。普通B-ALL组患者E-钙黏蛋白表达水平高于其他免疫表型的B-ALL患者（P<0.01），而按法国-美国-英国（FAB）分型分组的患者之间未发现显著差异。通过对测量数据的相关性分析，发现E-钙黏蛋白表达水平较低与高白细胞计数和血清乳酸脱氢酶（LDH）水平相关（r=-0.419，r=-0.269），但在B-ALL中与低血小板计数相关（r=0.335）。在T-ALL中，发现E-钙黏蛋白表达与LDH及骨髓中幼稚细胞百分比呈负相关（r=-0.567，r=-0.557）。此外，初诊AML患者中E-钙黏蛋白表达较低也与白细胞计数及骨髓中幼稚细胞百分比相关（r=-0.368，r=-0.391）。与对照组相比，3种类型的AL患者中E-钙黏蛋白表达显著下调（P<0.01），而β-连环蛋白、Akt显著上调（P<0.01）。T-ALL中p-Akt及p-Akt/Akt表达显著上调（P<0.01）。
E-钙黏蛋白低表达是儿童急性白血病预后不良的相关因素。E-钙黏蛋白表达缺失或下调可能激活Wnt/β-连环蛋白和PI3K/Akt信号通路，促进血液系统恶性肿瘤的发生和发展，从而导致细胞一系列恶性生物学行为。E-钙黏蛋白可能是儿童急性白血病新的预后指标，从而指导个体化血液治疗。
