Dual BTK and MDM2 inhibition effects in microenvironment protected chronic lymphocytic leukemia cells

In B-chronic lymphocytic leukemia (B-CLL) the interaction between leukemic cells and the environmental niches confers drug resistance and promotes tumor cells survival. The Bruton?s tyrosine kinase inhibitor ibrutinib is one of the first-in-class molecules available for the treatment of B-CLL patients able to disrupt the microenvironment protection. However, the emerging mechanisms of resistance affecting patients? survival call for new therapeutic strategies. The purpose of the current study was to investigate the ability of ibrutinib plus the MDM2-inhibitor nutlin-3 to counteract the tumor microenvironment protective effect