Although the mechanisms of NOTCH1/NF-kappaB interaction in CLL are rather elusive [161], evidence in models of T-cell leukemia suggest the possibility of both a transcription-dependent interaction, through its target HES1 that, in turn, can modulate other components of NF-kappaB pathway [156], and a transcription-independent interaction, where NOTCH1 may directly interact with the p50/c-Rel subunit, to retain the active NF-kappaB heterodimer in the nucleus [162]. This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.