The immunoglobulin heavy chain gene 3' enhancers induce Bcl2 deregulation and lymphomagenesis in murine B cells.
Leukemia
; 25(9): 1484-93, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21606958
Human follicular B-cell lymphoma is associated with the t(14;18) chromosomal translocation that juxtaposes the Bcl2 proto-oncogene with the immunoglobulin heavy chain (Igh) locus, resulting in the deregulated expression of Bcl2. Our previous studies have shown that the Igh 3' enhancers deregulate the Bcl2 expression in vitro. However, the effects of the Igh 3' enhancer elements on Bcl2 expression in vivo are not known. To investigate the role of the Igh 3' enhancers in Bcl2 deregulation, we used gene targeting to generate knock-in mice in which four DNase I-hypersensitive regions from the murine Igh 3' region were integrated 3' of the Bcl2 locus. Increased levels of Bcl2 mRNA and protein were observed in the B cells of Igh-3'E-bcl2 mice. B cells from Igh-3'E-bcl2 mice showed an extended survival in vitro compared with B cells from wild-type (Wt) mice. The Bcl2 promoter shift from P1 (the 5' promoter) to P2 (the 3' promoter) was observed in B cells from Igh-3'E-bcl2 mice, similar to human t(14;18) lymphomas. The IgH-3'E-bcl2 mice developed monoclonal B-cell follicular lymphomas, which were slowly progressive. These studies show that the Igh 3' enhancers have an important role in the deregulation of Bcl2 and B-cell lymphomagenesis in vivo.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Linfoma de Células B
/
Proteínas Proto-Oncogénicas
/
Elementos de Facilitación Genéticos
/
Regiones no Traducidas 3'
/
Genes de las Cadenas Pesadas de las Inmunoglobulinas
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Leukemia
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido