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Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells

Oncogene volume 26, pages 3797–3810 (2007)Cite this article

Abstract

The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B) encodes a Krüppel-like zinc-finger protein, which plays a crucial role in thymopoiesis and has been associated with hematopoietic malignancies. It was hypothesized that BCL11B may act as a tumor-suppressor gene, but its precise function has not yet been elucidated. Here, we demonstrate that the survival of human T-cell leukemia and lymphoma cell lines is critically dependent on Bcl11b. Suppression of Bcl11b by RNA interference selectively induced apoptosis in transformed T cells whereas normal mature T cells remained unaffected. The apoptosis was effected by simultaneous activation of death receptor-mediated and intrinsic apoptotic pathways, most likely as a result of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) upregulation and suppression of the Bcl-xL antiapoptotic protein. Our data indicate an antiapoptotic function of Bcl11b. The resistance of normal mature T lymphocytes to Bcl11b suppression-induced apoptosis and restricted expression pattern make it an attractive therapeutic target in T-cell malignancies.

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Acknowledgements

We thank R Jack, J Sonnemann, J Beck, J Mayerle, FU Weiss and M Lerch from the University of Greifswald for helpful discussion and critical reading of the manuscript. This work was supported by the Alfried Krupp von Bohlen and Halbach Stiftung (PG, GKP, JB and CAS), the Committee for Scientific Research, Poland (Grant KBN 2 P05A 057 26; GKP), the German Josĕ Carreras Leukemia Foundation (PG, KA and CAS) and BMBF-NBL3 (PG, CAS and UV).

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Authors and Affiliations

  1. Clinic for Internal Medicine C, University of Greifswald, Greifswald, Germany

    P Grabarczyk, G K Przybylski, J Bahr, K Assmus & C A Schmidt

  2. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

    G K Przybylski

  3. Laboratory for Functional Genomics, University of Greifswald, Greifswald, Germany

    M Depke & U Völker

  4. Institute for Immunology and Transfusion Medicine, University of Greifswald, Greifswald, Germany

    B M Bröker

  5. Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Greifswald, Germany

    R Walther

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  1. P Grabarczyk
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Correspondence to C A Schmidt.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Grabarczyk, P., Przybylski, G., Depke, M. et al. Inhibition of BCL11B expression leads to apoptosis of malignant but not normal mature T cells. Oncogene 26, 3797–3810 (2007). https://doi.org/10.1038/sj.onc.1210152

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