Given the intricate interaction between NOTCH1, pre-TCR signaling and E proteins, we elected to use Cd3e-/- mice as a powerful genetic model to dissect and decouple the roles of NOTCH1, pre-TCR and HEB in leukemia progression, specifically in DN3 thymocytes, previously shown to be the cell of origin of SCL-LMO1 (2, 4) and LMO2 (48) -induced T-ALL. This evidence concerns the gene TAL1 and acute lymphoblastic leukemia.