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STAT3 contributes to NK cell recognition by modulating expression of NKG2D ligands in adriamycin-resistant K562/AO2 cells

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Abstract

Leukemic cells can survive after chemotherapy by acquisition of multidrug resistance genes, but other phenotypes related to escape from immune recognition remain elusive. Adriamycin-resistant K562/AO2 cells are less susceptible to elimination by NK cells compared with wild type K562 cells due to lower expression of NKG2D ligands. Treatment of K562/AO2 cells with STAT3 inhibitor VII resulted in reduced expression of multidrug resistance gene P-glycoprotein, and up-regulation of NKG2D ligands on K562/AO2 cells. Meanwhile, K562/AO2 cells treated with STAT3 inhibitor proliferated less and were more susceptible to killing by NK cells than untreated K562/AO2 cells. The enhanced cytotoxicity of NK cells against K562/AO2 cells was partly blocked by treatment of NK cells with anti-NKG2D antibodies. These data suggest that STAT3 contributes to NK cell recognition by modulating NKG2D ligands in K562/AO2 cells, which may a mechanism by which cells survive and cause relapse of leukemia.

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Acknowledgments

This work was supported by China Postdoctoral Science Foundation (20110491337), Postdoctoral Science Foundation of Jiangsu (1101012C), Major projects of Changzhou City Health Bureau (ZD201108), the Key Medical Subject Fundation of Jiangsu and Jiangsu Province ordinary higher education graduate innovation program (CXZZ13-0130).

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Authors and Affiliations

  1. Department of Hematology, The Key Medical Subject of Jiangsu, The Affiliated Hospital of Southeast University, Zhongda Hospital, Hunan Road Dingjia Qiao 87, Nanjing, 210009, China

    Xiaohui Cai, Xuzhang Lu & Baoan Chen

  2. Department of Hematology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, China

    Xuzhang Lu, Zhuxia Jia, Xiuwen Zhang, Wenmin Han, Xiao Rong, Lingdi Ma & Min Zhou

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  1. Xiaohui Cai
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  2. Xuzhang Lu
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  8. Min Zhou
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Correspondence to Xuzhang Lu.

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Cai, X., Lu, X., Jia, Z. et al. STAT3 contributes to NK cell recognition by modulating expression of NKG2D ligands in adriamycin-resistant K562/AO2 cells. Int J Hematol 102, 536–543 (2015). https://doi.org/10.1007/s12185-015-1860-7

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  • DOI: https://doi.org/10.1007/s12185-015-1860-7

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