Histone deacetylases as therapeutic targets in hematologic malignancies. Review uri icon

Overview

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.

publication date

  • July 1, 2002

Research

keywords

  • Enzyme Inhibitors
  • Hematologic Neoplasms
  • Histone Deacetylase Inhibitors

Identity

Scopus Document Identifier

  • 0036014986

Digital Object Identifier (DOI)

  • 10.1097/00062752-200207000-00010

PubMed ID

  • 12042707

Additional Document Info

volume

  • 9

issue

  • 4