EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation.
Cancer Cell
; 23(5): 677-92, 2013 May 13.
Article
en En
| MEDLINE
| ID: mdl-23680150
ABSTRACT
The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas. Here, we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GC B cell (GCB)-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell (ABC)-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Transformación Celular Neoplásica
/
Centro Germinal
/
Complejo Represivo Polycomb 2
/
Mutación
Límite:
Animals
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos