While TAL1 expression in T-ALL was linked with a late cortical stage of T cell differentiation on the basis of cell surface markers [38] or whole transcriptome [104], we provide cellular and genetic evidence that the initiating events occur in earlier stages in which NOTCH1 signals are highest, i.e. at the DN2b to DN3a transition, and that the Cd3ε gene is dispensable. Here, TAL1 is linked to acute lymphoblastic leukemia.