Abstract
Heritable gene regulatory information can be imparted through cytosine methylation of DNA and posttranslational modifications of histones and other chromatin proteins. These epigenetic instructions play a fundamental role in determining the phenotype of normal cells during tissue differentiation. Disruption of normal epigenetic programming plays an equally fundamental role in determining the phenotype of tumor cells in concert with genetic lesions, and is a hallmark of cancer. Aberrant distribution of cytosine methylation occurs in specific biologically and clinically relevant patterns in acute myeloblastic and lymphoblastic leukemias, and is particularly widespread in advanced stages of myelodysplasia. Both aberrant hypomethylation and hypermethylation appear to contribute to these abnormal patterns. Genomic analysis of aberrantly methylated genes provides clues towards which transcription factors direct gene expression in epigenetically defined leukemia subtypes. One difference between epigenetic and genetic lesions is that the former can be therapeutically erased or reprogrammed. Along these lines efforts to identify epigenetic biomarkers to guide epigenetic therapy has become of great interest, as has the development of novel drugs that target the various chromatin-modifying complexes. This presentation will explore state of the art data from various sources and discuss the biological and clinical significance, as well as therapeutic targeting of aberrant epigenetic programming in these diseases.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):ED03-03.
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