Histone deacetylases as therapeutic targets in hematologic... : Current Opinion in Hematology (original) (raw)
Hematologic malignancies
*Assistant Professor, Division of Hematology, and †Professor, Department of Medicine, Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York, USA.
Correspondence to Jonathan D. Licht, MD, Box 1130, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA; e-mail: [email protected]
Supported by R01 CA 59936 (Dr. Licht) and American Cancer Society Award DHP 160 (Dr. Licht). Dr. Melnick is supported by NCI K08 CA73762, the Chemotherapy Foundation, and the Sol Sloan Memorial Fund.
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.
© 2002 Lippincott Williams & Wilkins, Inc.