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Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia

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Abstract

Bcl-2-associated athanogene 3 (BAG3), a member of BAG family, is shown to sustain cell survival and underlie resistance to chemotherapy in human neoplastic cells. We aimed to determine the exact role and underlying mechanisms of BAG3 in human chronic lymphocytic leukemia (CLL). One hundred human CLL samples and 20 normal B-cell samples from healthy controls were collected. We measured the BAG3 expression in these cells and explored its relationship with known prognostic factors for CLL. The roles of BAG3 in cell apoptosis and migration were evaluated by small interfering RNA-mediated knockdown of BAG3 in primary CLL cells. We showed that BAG3 expression level was increased in CLL cells compared with normal B cells. Moreover, BAG3 expression was particularly upregulated in CD38 positive, unmutated immunoglobulin heavy-chain patients and those with lymphadenopathy and/or splenomegaly. Importantly, patients with increased BAG3 expression level have poor overall survival in subgroups with positive ZAP-70 or those without any “p53 abnormality”. In addition, knocking down of BAG3 expression resulted in increased apoptotic ratio and decreased migration in primary CLL cells. Our data indicate that BAG3 is a marker of poor prognostic in specific subgroups of CLL patients and may be a potential therapeutic target for this disease.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (81170486, 81170485, 30871104, 30971296, 81000216, 81170488, 81100352), Jiangsu Province’s Medical Elite Program (RC2011168), the International Cooperation Program of Jiangsu Province (BZ2010041), Key Project of Jiangsu Province Health Agency (K201107, K201108), Natural Science Fund for Distinguished Young Scholars of Jiangsu Province (2013-32 to Prof. Peng Liu), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (JX10231801), National Public Health Grand Research Foundation (201202017), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, Jiangsu Province Higher Education Institute Foundation of Science and Technology Innovation Team Program and the Project for State Key Clinical Department construction.

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Rd, Nanjing, 210029, China

    Huayuan Zhu, Wei Wu, Yuan Fu, Wenyi Shen, Kourong Miao, Min Hong, Wei Xu, Peng Liu & Jianyong Li

  2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ken H. Young

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  1. Huayuan Zhu
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  2. Wei Wu
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  3. Yuan Fu
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Correspondence to Peng Liu or Jianyong Li.

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Zhu, H., Wu, W., Fu, Y. et al. Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia. Ann Hematol 93, 425–435 (2014). https://doi.org/10.1007/s00277-013-1883-1

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  • DOI: https://doi.org/10.1007/s00277-013-1883-1

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