Using a panel of 28 hematological cancer cell lines and more than 350 primary samples we identify AML-specific AWT1 promoter hypermethylation that is present irrespective of underlying translocation/oncogenic fusion protein or mutations, which is accompanied by a concomitant epigenetic switch at the level of post-translational histone tail modifications. This evidence concerns the gene WT1 and acute myeloid leukemia.