In this preclinical study, we assessed the IRAK4 inhibitor emavusertib (CA4948) in combination with the MCL1 inhibitor S63845, the BCL2 inhibitor venetoclax, and the HSP90 inhibitor PU-H71 in the treatment of acute myeloid leukemia and investigated the associated biomarkers of response. Here, MCL1 is linked to acute myeloid leukemia.