NOTCH1 and acute lymphoblastic leukemia: Mechanistically, disruption or deletion of the PEST domain can be found in 15% T-ALL and has a relationship with FBW7 mutation, causing increased intracellular Notch1 (ICN1) protein stabilization; heterodimeric domain point mutation can be found in 25% T-ALL and has a relationship with PEST or FBW7 mutations, contributing to ligand-independent activation of the receptor (Weng et al., 2004).