Here we asked whether the genome-wide positioning of H3K9me2 is altered in the human AML cells as opposed to the normal process of H3K9me2 spreading during myeloid differentiation, do these changes include any specific genomic regions showing gains or loss of H3K9me2 in all or certain types of AML, are these changes associated with coordinated transitions in gene expression and/or genomic instability, and whether these changes, especially those specific for AML, could be reversed by pharmacological targeting of G9a/GLP. Here, EHMT2 is linked to acute myeloid leukemia.