E-cadherin Expression In Children With Acute Leukemia And Its Clinical Significance

Objective: To investigate the correlation between the expression level of E-cadherin mRNA and the clinical characteristics in children with acute leukemia(AL)and explore the possible regulatory mechanism.Methods: Real-time quantitative RT-PCR was applied to detect the mRNA 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 protein expression levels of E-cadherin,?-catenin,and Akt/p-Akt were detected using Western blotting.The bone marrow samples from 22 children without malignant hematological disorders were used as controls.Results: The expression level of E-cadherin significantly decreased in bone marrow samples from newly diagnosed patients with either types of AL patients compared to bone marrow samples from control group(all P<0.01).In B-ALL group,compared with standard risk group,E-cadherin expression level significantly decreased in intermediate risk group(P=0.022).Moreover,the expression level of E-cadherin mRNA alsodecreased in splenomegaly group(P=0.001).However,no relevance between E-cadherin level and clinical characteristics was found in T-ALL and AML(P>0.05).In patients from Common-B-ALL group,the higher expression level of E-cadherin was observed compared to B-ALL patients with other immunophenotypes(P<0.01),while no obvious difference was shown among patients grouped by FAB classification.The linear correlation analysis of measurement data,lower E-cadherin expression level was found associated with high white blood cell(WBC)counts and serum lactic dehydrogenase level(LDH)(r=-0.440,r=-0.269),whereas related with low blood platelet counts 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=-0.557,r=-0.567).In addition,the expression of E-cadherin was also found having the trend negatively correlated with WBC and percentage of immature cells in the bone marrow in newly diagnosed AML patients(r=-0.368,r=-0.401).Compared with control group,the protein expression of E-cadherin was down-regulated significantly(P<0.0001),while ?-catenin and Akt levels were significantly up-regulated in either of three types of AL patients(P<0.01).Besides,p-Akt and p-Akt/Akt ratio were up-regulated significantly in T-ALL(P<0.0001).Conclusion: Lower expression of E-cadherin was relevant factor of unfavourable prognosis in children with acute leukemia.The expressiondeficiency or down-regulation of E-cadherin may activate Wnt/?-catenin and PI3K/Akt signaling pathways to promote development and progression of haematological malignancies and result in a series of malignant biological behaviors in cells.E-cadherin may be a new biomarker for prognosis of pediatric acute leukemia and an index to guide individualized chemotherapy.