TP53 and B-cell chronic lymphocytic leukemia: In this scenario, we previously demonstrated that the combination of ibrutinib with MDM2-inhibitors synergized in promoting apoptosis in B-CLL cell lines carrying wild-type p53 as well as 17p13 deletion and/or TP53 mutations [16], and that ibrutinib combined with gamma-secretase inhibitors exhibited enhanced cytotoxicity that was coupled with the down-regulation of the c-MYC oncogene [8].