Methylated DNA immunoprecipitation followed by high-throughput sequencing 
(MeDIP-seq) has the potential to identify changes in DNA methylation important 
in cancer development. In order to understand the role of epigenetic modulation 
in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to 
the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed 
leukemia-associated differentially methylated regions that included gene 
promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and 
DPP6) with significantly methylated promoters were of interest and further 
analysis of their expression showed them to be repressed in AML. We also 
demonstrated considerable cytogenetic subtype specificity in the methylomes 
affecting different genomic features. Significantly distinct patterns of 
hypomethylation of certain interspersed repeat elements were associated with 
cytogenetic subtypes. The methylation patterns of members of the SINE family 
tightly clustered all leukemic patients with an enrichment of Alu repeats with a 
high CpG density (P<0.0001). We were able to demonstrate significant inverse 
correlation between intragenic interspersed repeat sequence methylation and gene 
expression with SINEs showing the strongest inverse correlation (R(2) = 0.7). We 
conclude that the alterations in DNA methylation that accompany the development 
of AML affect not only the promoters, but also the non-promoter genomic 
features, with significant demethylation of certain interspersed repeat DNA 
elements being associated with AML cytogenetic subtypes. MeDIP-seq data were 
validated using bisulfite pyrosequencing and the Infinium array.