TY - JOUR
T1 - Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies
AU - Bhalla, Kapil N.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2005.16.600
DO - 10.1200/JCO.2005.16.600
M3 - Review article
C2 - 15897549
AN - SCOPUS:21244467166
VL - 23
SP - 3971
EP - 3993
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 17
ER -