A paradoxical tumor suppressor role for the Rac1 exchange factor Vav1 in early cortical T cell acute lymphoblastic leukemia

Robles-Valero et al. report a tumor suppression role for the otherwise oncogenic Vav1 Rho GEF. This paradoxical action is mediated by the catalysis-independent buffering of Notch1 signaling in immature T cells. These data reverse the long-held paradigm that Rho GEFs always favor tumor growth and unveil a new signaling crosstalk likely involved in human T-ALL etiology. DMBA was administered (0.1 ml - 10 mg/m) weekly via intragastric intubation to female mice of indicated genotypes for a total of six weeks. The first administration started when animals were 8-week-old. Mice were then examined weekly until showing obvious physical signs of sickness and thymi were collected