We propose a model whereby accumulation in the relapsing AMLs of hyper- or hypo-methylation at sparse CpGs of gene-bodies is the consequence of the selective pressure of chemotherapy on the epigenomic heterogeneity of primary leukemias, as generated by maintenance failures and aberrant expression of DNMT1 (epigenetic-instability at CpG-poor regions). Here, DNMT1 is linked to leukemia.