Much attention has been devoted to PTEN, since the initial report by Ferrando and coworkers documenting that PTEN gene expression was inactivated in T-ALL cell lines and patients displaying Notch-1 activating mutations, through a repressive mechanism mediated by Hairy and Enhancer of Split homolog-1 (HES-1) [137-139]. The gene discussed is PTEN; the disease is acute lymphoblastic leukemia.