We used converging genome-wide approaches together with molecular and genetic approaches to provide novel evidence how the necessary collaboration between SCL, LMO1 and Notch1 determines the target cells of transformation in T-ALL and to identify novel mechanisms by which these oncogenes cooperate to activate stem cell genes and to convert normal thymocytes into self-renewing pre-LSCs. This evidence concerns the gene NOTCH1 and acute lymphoblastic leukemia.