The progressive age-dependent accumulation of DN4 and DP thymocytes in the absence of pre-TCR/TCRb expression in NOD.Scid.Il15−/− mice is consistent with our previous work on TAL1-induced T-ALL, indicating that progression from a pre-leukemic DN3 stage to DP/SP8+ T-ALL requires the acquisition of a pre-TCR molecular signature, even in Cd3e-deficient mice that completely lack pre-TCR signaling [92]. Here, SP8 is linked to acute lymphoblastic leukemia.