In conclusion, N3tg/p50−/− double-mutant mice may represent a novel model to achieve a better understanding of how combined mutations of Notch and NF-κB1 may impact on both the progression of T-ALL and the composition of T-ALL immune-environment in the attempt to identify innovative multiple target therapy for the disease. The gene discussed is NFKB1; the disease is acute lymphoblastic leukemia.