Epigenetic modulation in hematologic malignancies: challenges and progress.

Abstract

Genetic alterations, including gene mutations, and chromosomal amplifications, deletions, inversions, and translocations, are hallmarks of the molecular biology of cancer. These events lead to oncogene activation, formation of chimeric oncoproteins, and/or inactivation of tumor suppressor genes. Such genetic changes contribute to the neoplastic transformation of cells, as well as the eventual acquisition by malignant cells of a more aggressive biologic and clinical behavior. However, in recent years, it has become apparent that these genetic events are not the sole determinants of the biologic behavior of tumor cells. Indeed, it is becoming increasingly apparent that tumor cells with a given genotype exhibit a differential phenotype depending on the microenvironment in which they reside. Furthermore, extensive data have shown that derivative daughter cells of neoplastic, as well as normal cells, inherit changes in the patterns of gene expression that are not associated with changes in the primary DNA sequence but are instead related to changes in chromatin structure and its accessibility for transcriptional activity. These heritable gene expression changes that are not associated with changes in the primary nucleotide sequence are referred to as epigenetic changes. This review provides an overview of the regulation of the "epigenome" in neoplastic cells, with particular emphasis on DNA methylation and histone acetylation as therapeutic targets for hematologic malignancies.

• Authors: Constantine S Mitsiades, Kenneth C Anderson
• Journal: Journal of the National Comprehensive Cancer Network : JNCCN (J Natl Compr Canc Netw) Vol. 7 Suppl 8 Pg. S1-12; quiz S14-6 (Nov 2009) ISSN: 1540-1405 [Print] United States
• PMID: 19930971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Histone Deacetylase Inhibitors

Topics

• CpG Islands
• DNA Methylation (drug effects)
• Epigenesis, Genetic (drug effects)
• Hematologic Neoplasms (drug therapy, genetics)
• Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
• Humans
• Prognosis