title: Haploinsufficiency of Bcl11b for suppression of lymphomagenesis and thymocyte development.
abstract: Recurrent chromosomal rearrangements at BCL11B are found in human hematopoietic malignancies mostly of T-cell origin. However, it is unclear how this disruption contributes to oncogenesis, because the majority of leukemias express BCL11B from an undisrupted allele. Here, we show that Bcl11b(+/-)p53(+/-) mice exhibited greater susceptibility to lymphomas than Bcl11b(+/+)p53(+/-) mice but most lymphomas retained and expressed the wild-type Bcl11b allele. This strongly suggests that Bcl11b is haploinsufficient for suppression of thymic lymphoma development in mice of the p53(+/-) background, a situation in which functional loss of only one allele confers a selective advantage for tumor growth. The haploinsufficiency is further supported by that Bcl11b(+/-) mouse embryos were impaired in thymocyte development and survival. These results indicate relevance of BCL11B aberration to human leukemogenesis.
authors.affiliation: Department of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata 951-8510, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kamimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kubota
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okazuka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Mishima
authors.forename: Ryo
authors.initials: R
authors.lastname: Kominami
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D005720:Gamma Rays; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D013953:Thymus Neoplasms / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: C511143:Bcl11b protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins