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01.03.2014 | Original Article

Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia

verfasst von: Huayuan Zhu, Wei Wu, Yuan Fu, Wenyi Shen, Kourong Miao, Min Hong, Wei Xu, Ken H. Young, Peng Liu, Jianyong Li

Erschienen in: Annals of Hematology | Ausgabe 3/2014

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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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Titel: Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia
verfasst von: Huayuan Zhu
Wei Wu
Yuan Fu
Wenyi Shen
Kourong Miao
Min Hong
Wei Xu
Ken H. Young
Peng Liu
Jianyong Li
Publikationsdatum: 01.03.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 3/2014
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-013-1883-1

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