In agreement with previous reports [15], we show that depletion of MYB reverses the leukaemia-associated cellular phenotypes in MLL-rearranged AML, which is accompanied by de-repression of MAFB. However, we find that AML with complex karyotypic lesions does not undergo the conventional transcriptional and morphological alterations that are associated with MYB suppression. Here, KMT2A is linked to acute myeloid leukemia.