Cunningham, T.J., Palumbo, I., Grosso, M., Slater, N. and Miles, C.G. (2013) WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio. Blood, 122(2), pp. 188-192. (doi: 10.1182/blood-2012-11-466086)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Slater, Dr Nicholas |
| Authors: | Cunningham, T.J., Palumbo, I., Grosso, M., Slater, N., and Miles, C.G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Blood |
| Publisher: | American Society of Hematology |
| ISSN: | 0006-4971 |
| ISSN (Online): | 1528-0020 |
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