The idea that p53 might be involved arose from the observations in another T-cell neoplasm, T-ALL, where hyperactivation of Notch-1 inhibits PTEN, which in turn leads to activation of Akt and p53 degradation via induction of human homolog of the mouse double minute 2 p53-binding protein (MDM2) (for a review see Dotto [35]). Here, NOTCH1 is linked to acute lymphoblastic leukemia.