In line with this hypothesis, we found that NOTCH3 inhibition by RO4929097, or more specifically, by siRNA, downregulated the NOTCH3/NR4A1 axis, enhanced the NOTCH2/FCER2 (CD23) axis, and counteracted apoptosis in CLL cells. Here, NR4A1 is linked to B-cell chronic lymphocytic leukemia.