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Cancer Res. 2017 Jan 15;77(2):482-493. doi: 10.1158/0008-5472.CAN-16-0842. Epub 2016 Oct 3.

EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance.

Zheng X1,2, Fan X1,2, Fu B1,2, Zheng M3, Zhang A4, Zhong K5, Yan J6, Sun R1,2, Tian Z7,2, Wei H7,2.

Author information

1
Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
2
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
3
The First Affiliated Hospital of Anhui Medical University, Hefei, China.
4
Anhui Provincial Hospital, Hefei, China.
5
High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China.
6
Department of Medical Technology, Anhui Medical College, Hefei, China.
7
Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China. ustcwhm@ustc.edu.cn tzg@ustc.edu.cn.

Abstract

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.

PMID:
27697766
DOI:
10.1158/0008-5472.CAN-16-0842
[Indexed for MEDLINE]
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