UNLABELLED: Acute megakaryoblastic leukemia driven by the RBM15-MKL1 fusion protein (RM-AMKL) is the only known recurrent mutation involving the N6-methyladenosine (m6A) writer complex. Dysregulation of m6A modification affects RNA fate and is linked to oncogenesis. Inhibition of m6A deposition via inhibition of the METTL3 writer protein has anti-tumour activity, but the mechanism underlying its efficacy and cancer specificity remains unclear. We treated murine RM-AMKL cells with a novel METTL3 inhibitor, STM3675, and showed apoptosis KEY POINTS: RM retains functional abilities of RBM15 and additionally interacts with Wnt-related transcripts to increase expression of Fzd proteins.The METTL3 writer complex and WNT signalling pathways are essential for RM-driven leukemia.