Lymphomas arising in Eμ-myc mice commonly bear mutations that inactivate the p19Arf/Mdm2/p53 pathway, either by p53 mutation or deletion, p19Arf deletion, or overexpression of Mdm2.51 Although expression of dominant-negative FoxO (dnFoxO) reduced selective pressure to inactivate the p19Arf/p53 pathway during lymphomagenesis in Eμ-myc mice,26 this was not the case for FoxO3−/−Eμ-myc lymphomas (Figure 8). This evidence concerns the gene MDM2 and lymphoma.