Originally published as JCO Early Release 10.1200/JCO.2005.16.600 on May 16 2005
Journal of Clinical Oncology, Vol 23, No 17 (June 10), 2005: pp. 3971-3993
© 2005 American Society of Clinical Oncology.
Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies
Kapil N. Bhalla
From the Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute University of South Florida, Tampa, FL
Address reprint requests to Kapil N. Bhalla, MD, Moffitt Cancer Center & Research Institute, 12902 Magnolia Dr, MRC 3 E, Room 3056, Tampa, FL 33612; e-mail: bhallakn{at}moffitt.usf.edu.
Epigenetic regulation of gene expression is mediated through alterations in the DNA methylation status, covalent modifications of core nucleosomal histones, rearrangement of histones, and by RNA interference. It is now abundantly clear that deregulation of epigenetic mechanisms cooperates with genetic alterations in the development and progression of cancer and leukemia. Epigenetic deregulation affects several aspects of tumor cell biology, including cell growth, cell cycle control, differentiation, DNA repair, and cell death. This raises the strong possibility that reversing deregulated epigenetic mechanisms may be an effective treatment strategy for leukemia and cancer. This treatment strategy may either be designed to separately or collectively target the specific perturbations in the epigenetic mechanisms found in human hematologic malignancies. The following review describes our current understanding of the important deregulated epigenetic mechanisms and the preclinical and clinical development of epigenetic and chromatin modifiers in the therapy of these disorders.
Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.
Author's disclosures of potential conflicts of interest are found at the end of this article.
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