Collectively, these data strongly suggest that inhibition of the anti-apoptotic canonical NOTCH2/CSL signaling (NOTCH2/FCER2 axis) by gliotoxin recovers a GSI sensitive pro-apoptotic non-canonical NOTCH3 function which may involve NFκB dependent NR4A1 expression (NOTCH3/NR4A1 axis) in CLL cells. Here, NR4A1 is linked to B-cell chronic lymphocytic leukemia.