Inhibiting the degradation of wild-type MLL using IRAK1/4 and IRAK4 inhibitors increased the stability of wild-type MLL in MLL-AF9 AML, which displaces the MLL fusion protein from some of its chromatin targets and leads to deregulation of the gene regulatory network in MLL-rearranged AML. Here, MLLT3 is linked to acute myeloid leukemia.