Here we investigated the combined treatment of PTC-596 with the MCL1-inhibitor S63845 and the MEK-inhibitor trametinib, as well as the p53 activator APR-246 on AML cells in order to identify a potentially effective treatment specifically for aggressive AML, in particular in patients with refractory disease and in patients unfit for intensive chemotherapy. Here, TP53 is linked to acute myeloid leukemia.