Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53.
Genes Dev
; 28(1): 58-70, 2014 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-24395247
ABSTRACT
The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteína p53 Supresora de Tumor
/
Proteínas Proto-Oncogénicas c-myc
/
Proteína 1 de la Secuencia de Leucemia de Células Mieloides
/
Linfoma
/
Mutación
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Genes Dev
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2014
Tipo del documento:
Article