NOTCH1 and acute lymphoblastic leukemia: Remarkably, the majority of insertions occurred within the HD and PEST domains of Notch-1, sites that are hotspots for somatic mutation in a high proportion of human T-ALL cases, highlighting the relevance of such approaches to human biology (Girard et al., 1996; Hoemann et al., 2000; Weng et al., 2004).