The possibility that NOTCH1 activates NF-kappaB in CLL was suggested by early evidence [6] which reported a higher degree of NF-kappaB-binding to its consensus sequence by electrophoretic mobility shift assay; further studies seemed to confirm these observations, evidencing the activation of the NF-kappaB pathway especially in the context of NOTCH1-mutated CLL cases, in which the activity of NICD was enhanced due to its prolonged half-life [160]. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.