Taking a step further, we posit that the loss of MLL1 enzymatic activity may be an unifying feature of leukemias with and without MLL1 translocations, including AML resulting from a partial tandem duplication in the MLL1 gene, where it has been shown that expression of the WT allele is epigenetically silenced in patient MLL1-PTD leukemic blasts (97), and in patient samples in which both MLL1 alleles have been deleted (43). This evidence concerns the gene KMT2A and acute myeloid leukemia.