文章：

儿童T细胞急性淋巴母细胞白血病中WNT信号失调

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

原文发布日期：2014-03-14

DOI: 10.1038/bcj.2014.12

类型: Original Article

开放获取: 是

英文摘要：

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated β-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When β-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

摘要翻译： 

WNT信号通路已被证实参与造血干细胞的调控，并在胸腺T细胞发育过程中发挥重要作用。本研究探讨了儿童T细胞急性淋巴细胞白血病（T-ALL）患者中WNT通路的激活状况。为评估WNT信号在T细胞白血病发生中的潜在作用，我们对WNT通路关键组分进行了表达分析。与正常人胸腺细胞相比，超过85%的儿童T-ALL患者在蛋白水平表现出β-连环蛋白表达上调。这种上调的影响体现在已知靶基因（AXIN2、c-MYC、TCF1和LEF）的高表达上。特别是AXIN2——WNT通路的通用靶基因，在约40%的患者中呈现mRNA和蛋白水平的双重上调。当通过小干扰RNA沉默β-连环蛋白基因后，癌细胞表现出更高的凋亡率。这些结果表明，异常WNT信号激活在相当比例的人类T-ALL病例中发生，且独立于已知的T-ALL风险因素。我们得出结论：失调的WNT信号通路是儿童T-ALL中一种新的致癌事件。

原文链接：

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia