Abstract
Epigenetics play a critical role in controlling normal gene expression and altered epigenetics can lead to abnormal cellular differentiation, proliferation and survival. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and is characterized by numerous epigenetic abnormalities. These epigenetic changes correspond to repressed activity of some genes and inappropriate activation of others. In contrast to genetic alterations stemming from mutations, deletions or translocation, epigenetic changes are relatively reversible when treated with certain small molecule-based anticancer agents. Histone deacetylase inhibitors (HDI) are a class of drugs capable of modifying the epigenetic status of ALL cells. Several recent preclinical and clinical studies have demonstrated the potential of HDI as therapeutic agents in ALL. This review summarizes recent studies on (1) the principles of epigenetics and their importance in ALL tumorigenesis; (2) the structure, mechanism of action and anti-tumor activity of HDI; (3) the first comprehensive summary of data from preclinical and clinical studies for HDI as the therapeutic agents for ALL; and (4) novel directions for future research on HDI and ALL.
Keywords: Leukemia, epigenetics, histone deacetylase inhibitors, therapeutic agent, anticancer agent, Choroid Lymphocytic Leukemia, Deoxyribonucleic Acid, Histone Methyl Transferases, Myeloid Cell Leukemia, Suberoylanilide Hydroxamic Acid
Current Cancer Drug Targets
Title: Targeting Epigenetics through Histone Deacetylase Inhibitors in Acute Lymphoblastic Leukemia
Volume: 11 Issue: 7
Author(s): A. Mummery, A. Narendran and K.-Y. Lee
Affiliation:
Keywords: Leukemia, epigenetics, histone deacetylase inhibitors, therapeutic agent, anticancer agent, Choroid Lymphocytic Leukemia, Deoxyribonucleic Acid, Histone Methyl Transferases, Myeloid Cell Leukemia, Suberoylanilide Hydroxamic Acid
Abstract: Epigenetics play a critical role in controlling normal gene expression and altered epigenetics can lead to abnormal cellular differentiation, proliferation and survival. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and is characterized by numerous epigenetic abnormalities. These epigenetic changes correspond to repressed activity of some genes and inappropriate activation of others. In contrast to genetic alterations stemming from mutations, deletions or translocation, epigenetic changes are relatively reversible when treated with certain small molecule-based anticancer agents. Histone deacetylase inhibitors (HDI) are a class of drugs capable of modifying the epigenetic status of ALL cells. Several recent preclinical and clinical studies have demonstrated the potential of HDI as therapeutic agents in ALL. This review summarizes recent studies on (1) the principles of epigenetics and their importance in ALL tumorigenesis; (2) the structure, mechanism of action and anti-tumor activity of HDI; (3) the first comprehensive summary of data from preclinical and clinical studies for HDI as the therapeutic agents for ALL; and (4) novel directions for future research on HDI and ALL.
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Mummery A., Narendran A. and Lee K.-Y., Targeting Epigenetics through Histone Deacetylase Inhibitors in Acute Lymphoblastic Leukemia, Current Cancer Drug Targets 2011; 11 (7) . https://dx.doi.org/10.2174/156800911796798922
DOI https://dx.doi.org/10.2174/156800911796798922 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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