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 non-malignant 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 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).
Conclusion: 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.
题目: E-cadherin基因在儿童急性白血病中的表达及其临床意义.
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-B-ALL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。.