The frequent occurrence of activating mutations of the NOTCH1 gene in T-ALL patients [129] and in mouse models of the disease [110,130], as well as the sensitivity of both human [52,56] and murine leukemic blasts [131] to NOTCH1 inhibitors, strongly indicates that a gain of function of NOTCH1 represents a critical step in cell transformation. This evidence concerns the gene NOTCH1 and acute lymphoblastic leukemia.