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

Authors:
Grabarczyk P, Przybylski GK, Depke M, Volker U, Bahr J, Assmus K, Broker BM, Walther R, Schmidt CA
In:
Source: Oncogene
Publication Date: (2007)
Issue: 26(26): 3797-810
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Jurkat
Species: human
Tissue Origin: blood
T cell, human peripheral blood unstim.
Species: human
Tissue Origin: blood
Raji
Species: human
Tissue Origin:
HuT 78
Species: human
Tissue Origin: blood
Platform:
Nucleofector™ I/II/2b
Abstract
The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B) encodes a KrĂĽppel-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.