A large amount of data, either from patients' studies or experimental models, supports the hypothesis of sustained antigen-dependent stimulation of BCR as a promoting event for clonal amplification of CLL cells.1, 10, 60 The sustained engagement of the BCR activates downstream targets such as NFkB, AKT and ERK,61, 62 which promote the expression of anti-apoptotic proteins, mainly BCL2 and MCL1.36, 63. Here, BCL2 is linked to B-cell chronic lymphocytic leukemia.