title: Targeting epigenetics through histone deacetylase inhibitors in acute lymphoblastic leukemia.
abstract: Epigenetics play a critical role in controlling normal gene expression and altered epigenetics can lead to abnormal cellular differentiation, proliferation and survival. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and is characterized by numerous epigenetic abnormalities. These epigenetic changes correspond to repressed activity of some genes and inappropriate activation of others. In contrast to genetic alterations stemming from mutations, deletions or translocation, epigenetic changes are relatively reversible when treated with certain small molecule-based anticancer agents. Histone deacetylase inhibitors (HDI) are a class of drugs capable of modifying the epigenetic status of ALL cells. Several recent preclinical and clinical studies have demonstrated the potential of HDI as therapeutic agents in ALL. This review summarizes recent studies on (1) the principles of epigenetics and their importance in ALL tumorigenesis; (2) the structure, mechanism of action and anti-tumor activity of HDI; (3) the first comprehensive summary of data from preclinical and clinical studies for HDI as the therapeutic agents for ALL; and (4) novel directions for future research on HDI and ALL.
authors.affiliation: Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Mummery
authors.forename: A
authors.initials: A
authors.lastname: Narendran
authors.forename: K-Y
authors.initials: KY
authors.lastname: Lee
mesh_terms: D044127:Epigenesis, Genetic / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases