RRC ID 35692
Author Kurosawa N, Fujimoto R, Ozawa T, Itoyama T, Sadamori N, Isobe M.
Title Reduced level of the BCL11B protein is associated with adult T-cell leukemia/lymphoma.
Journal PLoS One
Abstract BACKGROUND:Adult T-cell leukemia/lymphoma (ATLL) develops in a small proportion of human T-cell leukemia virus type I (HTLV-I)-infected individuals. However, the mechanism by which HTLV-I causes ATLL has not been fully elucidated. To provide fundamental insights into the multistep process of leukemogenesis, we have mapped the chromosomal abnormalities in 50 ATLL cases to identify potential key regulators of ATLL.
RESULTS:The analysis of breakpoints in one ATLL case with the translocations t(14;17)(q32;q22-23) resulted in the identification of a Kruppel zinc finger gene, BCL11B, which plays a crucial role in T-cell development. Among the 7 ATLL cases that we examined by immunofluorescence analysis, 4 displayed low and one displayed moderate BCL11B signal intensities. A dramatically reduced level of the BCL11B protein was also found in HTLV-I-positive T-cell lines. The ectopic expression of BCL11B resulted in significant growth suppression in ATLL-derived cell lines but not in Jurkat cells.
CONCLUSIONS:Our genetic and functional data provide the first evidence that a reduction in the level of the BCL11B protein is a key event in the multistep progression of ATLL leukemogenesis.
Volume 8(1)
Pages e55147
Published 2013-1-1
DOI 10.1371/journal.pone.0055147
PII PONE-D-12-19740
PMID 23383087
PMC PMC3559337
MeSH Base Sequence Cell Line, Tumor Cell Proliferation Cell Transformation, Viral Chromosome Breakpoints DNA Methylation / genetics Gene Expression Regulation, Neoplastic* Genetic Loci / genetics Human T-lymphotropic virus 1 / physiology Humans Leukemia-Lymphoma, Adult T-Cell / genetics* Leukemia-Lymphoma, Adult T-Cell / pathology Leukemia-Lymphoma, Adult T-Cell / virology RNA, Messenger / genetics RNA, Messenger / metabolism Repressor Proteins / biosynthesis Repressor Proteins / genetics* Repressor Proteins / metabolism* Translocation, Genetic / genetics Tumor Suppressor Proteins / biosynthesis Tumor Suppressor Proteins / genetics* Tumor Suppressor Proteins / metabolism*
IF 2.74
Times Cited 9
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).