In summary, we uncover a TET1/GFI1/EZH2/SIN3A⊣miR-22⊣CREB-MYC signalling circuit in de novo AML, in which miR-22 functions as a pivotal anti-tumour gate-keeper, distinct from its oncogenic role reported in MDS or MDS-derived AML16. This evidence concerns the gene GFI1 and myelodysplastic syndrome.