Ligand-independent NOTCH1 activation has been reported to be caused by aberrant recombination mediated by RAG2 that generates truncated NOTCH1 [101] or the activation of a cryptic internal promoter in Ikaros-deficient cells [102], both generating a functional ICN1 that is constitutively active, leading to the development of T-ALL. Here, NOTCH1 is linked to acute lymphoblastic leukemia.