A search for an alternative to GSI revealed that the Aspergillum-derived secondary metabolite gliotoxin is a potent inhibitor of DNA-bound NOTCH2/CSL transcription factor complexes, and efficiently induced apoptosis in CLL lymphocytes and in NOTCH2-associated solid tumor cell lines—independent of their sensitivity to GSIs [32,51]. Here, NOTCH2 is linked to B-cell chronic lymphocytic leukemia.