The Notch1/c-Myc pathway in T cell leukemia

The Notch receptor family and its ligands ( Delta - like and Jagged) have been found deregulated in several human cancers. We and the Aster/ Pear group recently identi fied c - myc as a direct transcriptional target gene of the Notch1 pathway in T cell acute lymphoblastic leukemia ( T - ALL). Although the oncogenic roles of c - Myc and Notch1 are established, a direct link between Notch1 and c - Myc had not been demonstrated. Importantly, our work in mouse tal1 tumor cell lines revealed that leukemic growth/ survival remains dependent on the Notch1 - c - Myc pathway. Studies by the Efstratiadis group provide genetic evidence that the Notch1 - c - Myc pathway also contributes to mouse mammary tumorigenesis. Taken together, these studies demonstrate that Notch1 mediates T cell and epithelial cell transformation at least in part by sustaining c - Myc levels.