TitleHistone deacetylases as therapeutic targets in hematologic malignancies.
Publication TypeJournal Article
Year of Publication2002
AuthorsMelnick, Ari, and Licht Jonathan D.
JournalCurr Opin Hematol
Volume9
Issue4
Pagination322-32
Date Published2002 Jul
ISSN1065-6251
KeywordsAnimals, Disease Models, Animal, Enzyme Inhibitors, Forecasting, Hematologic Neoplasms, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Isoenzymes
Abstract

<p>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.</p>

DOI10.1097/00062752-200207000-00010
Alternate JournalCurr Opin Hematol
PubMed ID12042707
Grant ListK08 CA73762 / CA / NCI NIH HHS / United States
R01 CA 59936 / CA / NCI NIH HHS / United States