title: Histone deacetylases as therapeutic targets in hematologic malignancies.
abstract: During the past 5 years, it has become increasingly apparent that deregulated transcriptional control is a root cause of hematologic malignancy. Chromosomal translocations yield novel fusion transcription factors that in turn either activate genes critical for cell growth or repress genes important for normal cellular differentiation. Many of the fusion proteins of myeloid leukemia are aberrant transcriptional repressors and share the property of recruiting histone deacetylases (HDACs) to target genes. HDACs, by acting on chromatin and on transcription factors themselves, can modulate gene regulation. HDACs also play major roles in the function of well-characterized tumor suppressors such as p53 and Rb. Thus, HDACs are a compelling therapeutic target for cancer therapy. Several classes of HDAC inhibitors induce differentiation and cell death in myeloid and lymphoid model systems. Some of these are now in clinical trials for hematologic malignancies. The nature of HDAC function, the classes of inhibitors available, and recent experimental and clinical data will be reviewed.
authors.affiliation: Division of Hematology, Department of Medicine, Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Licht
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005544:Forecasting; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D006655:Histone Deacetylases