儿童急性淋巴细胞白血病中E-钙黏蛋白甲基化对预后的影响

Influence of E-cadherin methylation on prognosis in children with acute lymphoblastic leukemia

摘要:

目的 检测儿童急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）患儿骨髓单个核细胞中E-钙黏蛋白（E-cadherin）mRNA及蛋白水平表达和基因甲基化状态，探讨E-cadherin在儿童ALL的意义及甲基化状态与预后的关系。方法 采集42例初次确诊的ALL患儿确诊时（治疗前组）及诱导化疗第33天（治疗后组）的骨髓血5 mL，应用RT-qPCR、Westerm blot及甲基化特异性PCR法检测骨髓单个核细胞中E-cadherin mRNA及蛋白表达和E-cadherin基因甲基化水平，并比较治疗前后各指标的变化。结果 治疗后组E-cadherin mRNA及蛋白的表达水平均高于治疗前组（P<0.05）；治疗后组E-cadherin基因甲基化阳性率较治疗前组下降（P<0.05）；至试验终点时，甲基化阴性者总生存率和无事件生存率均高于甲基化阳性者（P<0.05）。结论 E-cadherin表达与儿童ALL发展相关，表达降低及甲基化水平增高可能提示预后不良。

Abstract:

Objective To study the significance of E-cadherin and the association between E-cadherin methylation status and prognosis in children with acute lymphoblastic leukemia (ALL) by examining the mRNA and protein expression of E-cadherin and its gene methylation status in bone marrow mononuclear cells of children with ALL.Methods The samples of 5 mL bone marrow blood were collected from 42 children with ALL who were diagnosed for the first time at diagnosis (pre-treatment group) and on day 33 of induction chemotherapy (post-treatment group). RT-qPCR, Western blot, and methylation-specific PCR were used to measure the mRNA and protein expression of E-cadherin and the methylation level of the E-cadherin gene. The changes in each index after induction chemotherapy were compared.Results The mRNA and protein expression levels of E-cadherin in the post-treatment group were significantly higher than those in the pre-treatment group (P<0.05), while the positive rate of E-cadherin gene methylation in the post-treatment group was significantly lower than that in the pre-treatment group (P<0.05). At the end of the test, the children with negative methylation had significantly higher overall survival rate and event-free survival rate than those with positive methylation (P<0.05).Conclusions E-cadherin expression is associated with the development of ALL in children, and its decreased expression and increased methylation level may indicate a poor prognosis.