1. ¹Clinic for Internal Medicine C, University of Greifswald, Greifswald, Germany
2. ²Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
3. ³Laboratory for Functional Genomics, University of Greifswald, Greifswald, Germany
4. ⁴Institute for Immunology and Transfusion Medicine, University of Greifswald, Greifswald, Germany
5. ⁵Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Greifswald, Germany

Correspondence: Professor CA Schmidt, KIM C, Molecular Haematology, Universität Greifswald, Sauerbruchstr., Greifswald 17475, Germany. E-mail: christian.schmidt@uni-greifswald.de

Received 1 February 2006; Revised 29 September 2006; Accepted 23 October 2006; Published online 18 December 2006.

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.