KMT2A and acute myeloid leukemia: In summary, we conclude that IRF8 and MEF2D are context-specific transcriptional addictions of KMT2A-rearranged AML, where IRF8 directly activates transcription of MEF2D, while direct targets of MEF2D include key leukemogenic TFs HOXA9 and MYC (Fig. 7H).