文章：

Twist1过表达在原发急性髓系白血病中的良好临床结局及独特特征

Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia

原文发布日期：2015-08-14

DOI: 10.1038/bcj.2015.67

类型: Original Article

开放获取: 是

英文摘要：

Epithelial–mesenchymal transition (EMT) is a critical process for inducing stem-like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1, an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1, and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1. AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1-overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest that, in a subset of AML patients, Twist1 has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes.

摘要翻译： 

上皮-间质转化（EMT）是诱导上皮癌细胞获得干细胞样特性的关键过程。然而，EMT诱导因子在血液系统恶性肿瘤中的作用尚不明确。Twist1作为细胞迁移必需的EMT诱导因子，近期被发现对Bmi1表达具有转录调控活性，二者能够协同促进肿瘤发生。鉴于Bmi1表达对白血病干细胞的维持至关重要，我们推测Twist1可能同样调控急性髓系白血病（AML）的发病机制。研究发现，上调Twist1可增加AML中Bmi1的表达，赋予白血病细胞更强的增殖潜能和抗凋亡能力。在原发性AML样本中，Twist1与Bmi1表达水平呈显著正相关。白血病母细胞过度表达Twist1的AML患者临床表现更具侵袭性，但接受标准化治疗后更可能获得良好临床结局。体外研究证实，过表达Twist1的白血病细胞对阿糖胞苷的细胞毒性更敏感，但对柔红霉素无此效应。我们的研究结果表明，在部分AML患者中，Twist1通过介导独特临床表现的发病机制发挥重要作用。

原文链接：

Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia