WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio.
Blood
; 122(2): 188-92, 2013 Jul 11.
Article
en En
| MEDLINE
| ID: mdl-23699597
ABSTRACT
Mutations in the Wilms tumor suppressor 1 (WT1) gene are as frequent in acute myeloid leukemia (AML) as in nephroblastma and predict poor prognosis. However, the role of WT1 in hematopoiesis remains unclear. We show that Wt1-deficient mouse embryonic stem cells exhibit reduced hematopoietic potential caused by vascular endothelial growth factor A (Vegf-a)-dependent apoptosis of hematopoietic progenitor cells associated with overproduction of the Vegf-a120 isoform. We demonstrate that Wt1 promotes exon inclusion using a Vegf-a minigene-based splicing assay. These data identify a critical role for Wt1 in hematopoiesis and Vegf-a as a cellular RNA whose splicing is potentially regulated by Wt1. The correction of Wt1 deficiency by treatment with exogenous Vegf-a protein indicates that the Wt1/Vegf-a axis is a molecular pathway that could be exploited for the management/treatment of poor prognosis AMLs.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Empalme Alternativo
/
Proteínas WT1
/
Factor A de Crecimiento Endotelial Vascular
/
Hematopoyesis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido