American Association for Cancer Research
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Supplementary Figures from EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance

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posted on 2023-03-31, 00:46 authored by Xiaohu Zheng, Xiaolei Fan, Binqing Fu, Meijuan Zheng, Aimei Zhang, Kai Zhong, Jialai Yan, Rui Sun, Zhigang Tian, Haiming Wei

Supplementary Figure 1. Immunofluorescence and flow cytometry staining for EpCAM in leukemia and normal samples and leukemia cell lines. Supplementary Figure 2. Microarray analysis of markedly up-regulated genes in EpCAM-high cells relative to EpCAM-low cells. Supplementary Figure 3. EpCAM-high K562 cells are similar to tumor stem cells. Supplementary Figure 4. Analysis of AE7 specificity by flow cytometry and IHC/IF staining. Supplementary Figure 5. Analysis of the anti-tumor effect of EpCAM antibody in vivo (lung cancer, positive control) and in vitro. Supplementary Figure 6. Analysis of macrophage clearance after clodronate liposome injection by IF staining.

Funding

Natural Science Foundation of China

China Postdoctoral Science Foundation

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ARTICLE 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.

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