The strong association between surface NOTCH3 expression and apoptosis suggests that NOTCH3 signaling is involved in the execution phase of CLL cell apoptosis by prolonging the expression of the newly identified NOTCH3 target gene NR4A1, a multi-functional tumor-suppressor gene implicated in the regulation of B-cell tolerance to self-antigens [52,53,54]. Here, NR4A1 is linked to B-cell chronic lymphocytic leukemia.