NOTCH1 and acute lymphoblastic leukemia: In human T-ALL, most gain-of-function mutations of NOTCH1 occur in the homodimerization domain (HD) that results in ligand-independent activation, or in the C-terminal PEST domain that regulates ubiquitination and proteasomal degradation of the intracellular portion of NOTCH1 (ICN1, also called NICD: Notch intracellular domain), which transduces NOTCH signaling [5,23].