More recent studies clearly demonstrate that TP53 apoptotic network is a primary mediator of resistance to BCL-2 inhibition in AML cells [28], and increased activities of TP53 through MDM2 inhibition negatively regulates the RAS/RAF/MEK/ERK pathway and activates GSK3 to modulate MCL-1 phosphorylation and promote its degradation, thus overcoming AML resistance to BCL-2 inhibition by venetoclax [84]. This evidence concerns the gene BCL2 and acute myeloid leukemia.