In the mammalian blood system, for example, Notch1 mutations that remove an NICD degron sequence have been associated with increased NICD levels and the development of T-cell Acute Lymphoblastic Leukemia (T-ALL) in mice and humans (O'Neil et al., 2006; Weng et al., 2004). This evidence concerns the gene NOTCH1 and T-cell acute lymphoblastic leukemia.