EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance.
EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance.
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DOI：
10.1158/0008-5472.can-16-0842
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发表时间：
2017-01
期刊：
影响因子：
11.2
通讯作者：
Xiaohu Zheng;Xiaolei Fan;Binqing Fu;M. Zheng;Aimei Zhang;K. Zhong;Jialai Yan;R. Sun;Z. Tian-Z
中科院分区：
文献类型：
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作者：
Xiaohu Zheng;Xiaolei Fan;Binqing Fu;M. Zheng;Aimei Zhang;K. Zhong;Jialai Yan;R. Sun;Z. Tian-Z
缺乏有效的肿瘤相关抗原限制了髓系白血病靶向治疗的发展。在这项研究中，我们比较了急性髓性白血病（AML）和正常骨髓样本的基因表达模式，发现上皮细胞粘附分子（EpCAM）在AML患者中经常过表达，EpCAM+白血病细胞表现出增强的化疗耐药性和肿瘤发生。EpCAM阳性白血病细胞的化疗抗性是WNT 5 B信号传导增加的结果。此外，我们产生了EpCAM抗体，其分别能够通过巨噬细胞或自然杀伤细胞对AML细胞进行吞噬或细胞毒性。最后，EpCAM抗体治疗在皮下、播散和髓内移植的小鼠中耗尽AML。总之，EpCAM显示出作为治疗白血病的新靶点的前景。Cancer Res; 77（2）; 482-93.©2016 AACR.
The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling. Furthermore, we generated EpCAM antibodies that enabled phagocytosis or cytotoxicity of AML cells by macrophage or natural killer cells, respectively. Finally, EpCAM antibody treatment depleted AML in subcutaneous, disseminated, and intramedullary engrafted mice. In summary, EpCAM exhibits promise as a novel target for the treatment of leukemia. Cancer Res; 77(2); 482-93. ©2016 AACR.