Aberrant DNA methylation is a frequent event in the pathogenesis of various cancer types and is associated with reduced gene expression. Due to the limited knowledge about DNA methylation landscapes in chronic myeloid leukemia (CML), we conducted a genome-wide methylation study in the leukemia cell lines MO7e, MO7e/p210 and in normal bone marrow controls (nBM) by reduced-representation bisulfite sequencing (RRBS). In addition, we investigated gene expression using RNA-Sequencing (RNA-Seq) and

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... mpared RRBS data and RNA-Seq data. Overall, we observed higher CpG site methylation levels in cell lines compared to nBM and identified ~230.000 methylated CpG sites between MO7e/p210 and NBM. Moreover, we found ~2.000 differentially methylated CpG sites between MO7e/p210 and MO7e. While CpG sites with increased methylation were mainly located in CpG islands (CGIs) and CGI shores associated with promoter regions, CpG sites with decreased methylation were predominantly located within introns and intragenic regions in large distance to transcription start sites (TSS). By searching for enriched GO/MSigDB terms, we observed that genes with increased methylation in MO7e/p210 were mainly associated with developmental processes, cell differentiation and abnormal disease phenotypes. By contrast, genes with decreased methylation were mainly associated with angiogenesis. RNA-Seq analyses revealed that 442 genes are differentially expressed between MO7e/p210 and nBM. The majority of these genes was found to be downregulated in MO7e/p210 and included known/putative tumor suppressors and regulators of apoptosis, cell growth and cell adhesion. By comparison of DNA methylation and gene expression data, we identified genes with increased methylation, of which the majority was downregulated in MO7e/p210 compared to nBM. Within this gene cohort, we identified ~660 genes that were strongly downregulated in MO7e/p210 compared to MO7e and nBM. Many of these genes were found to be involved in apoptosis, cell adhesion and immune defense. Gene-sp [...]