title: EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance.
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. ©2016 AACR.
authors.affiliation: 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.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: 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.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Fan
authors.affiliation: 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.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Binqing
authors.initials: B
authors.lastname: Fu
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Anhui Provincial Hospital, Hefei, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhong
authors.affiliation: Department of Medical Technology, Anhui Medical College, Hefei, China.
authors.forename: Jialai
authors.initials: J
authors.lastname: Yan
authors.affiliation: 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.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: 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.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: 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.|Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000071858:Epithelial Cell Adhesion Molecule / Q000037:antagonists & inhibitors*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007157:Immunologic Surveillance / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019139:Tumor Escape / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule