Here, we used MSC-specific inducible Mettl3 knockout mice Prrx1-CreERT2;Mettl3fl/fl and an MLL-AF9 AML mouse model to define the influence of Mettl3 deficiency on AML progression, response to chemotherapy in vivo, and the underlying cellular and molecular pathways. This evidence concerns the gene PRRX1 and acute myeloid leukemia.