NOTCH1 and acute lymphoblastic leukemia: Notch1 is then cleaved by ADAM family metalloproteases (S2) and γ-secretase (S3) resulting in the release of the Notch1 intracellular domain (NICD), which translocates to the nucleus to promote transcription of target genes involved in cell growth.6, 7, 8, 9 The most frequent Notch1 mutations are observed in the heterodimerization (HD) and PEST domains.1, 2 Mutations of the HD domain allow a ligand-independent activation of the NICD promoting the uncontrolled growth of T-ALL cells.10