Despite having deciphered the entire human genetic code will still know little of how expression of the various genes is finely regulated so that only certain genes are expressed at the correct time and levels in specific cell types. Indeed on top of the primary sequence, epigenetic factors such as levels of chromatin packaging, histone modifications, and DNA methylation, contribute to the decision of switching genes on and off. Alterations in gene expression patterns accompany tumour progression, which is often associated with aberrant DNA methylation patterns. Both hypomethylation more prominent at repeat elements, and hyper-methylation of CpG islands are observed in cancer cells. Our published data indicate that antisense RNA transcription through a CpG island can induce its methylation. Similarly, antisense transcripts have been implicated in the methylation of CpG islands observed in imprinting and X-inactivation. We want to investigate whether such a mechanism underlies some of the methylation changes observed during tumourigenesis through the analysis of patients with haematopoietic malignancies. We have also developed a functional system to study the molecular details responsible for antisense-RNA mediated CpG island methylation. Understanding the basic mechanisms will provide us with invaluable tools for future development of better targeted therapies and drugs.