title: Reduced level of the BCL11B protein is associated with adult T-cell leukemia/lymphoma.
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.
authors: Faculty of Science and Engineering, Graduate School, University of Toyama, Toyama, Japan.
authors: Nobuyuki
authors: N
authors: Kurosawa
authors: Rika
authors: R
authors: Fujimoto
authors: Tatsuhiko
authors: T
authors: Ozawa
authors: Takahiro
authors: T
authors: Itoyama
authors: Naoki
authors: N
authors: Sadamori
authors: Masaharu
authors: M
authors: Isobe
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D056905:Chromosome Breakpoints; D019175:DNA Methylation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D014178:Translocation, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: C479740:BCL11B protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins
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