Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies
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 genet...
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| Veröffentlicht in: | Journal of clinical oncology 2005-06, Vol.23 (17), p.3971-3993 |
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| description | 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. |
| doi_str_mv | 10.1200/JCO.2005.16.600 |
| format | Article |
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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. 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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.</description><subject>Biological and medical sciences</subject><subject>Chromatin - genetics</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Silencing</subject><subject>Genetic Therapy</subject><subject>Histone Deacetylase Inhibitors</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Methyltransferases - metabolism</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - therapy</subject><subject>Promoter Regions, Genetic</subject><subject>Tumors</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtrGzEUhUVpaZyk6-7KbNqsxtGVRq9lMHm0JASKC90JWXNnrDAzcqUxJf8-MjZkdTbfOZf7EfIV6BIYpde_Vs_LkmIJcikp_UAWIJiqlRLiI1lQxVkNmv89I-c5v1AKjebiMzkDoY0SjVmQ37e70OOEc_CVm9pqtU1xdHOYqqfYhi5gytVNrtYu9ThjW623mNzutYpd9YAFjEPsS_XJDaGf3OQD5kvyqXNDxi-nvCB_7m7Xq4f68fn-5-rmsfYN43PdCM04U4xueCOYZJxTEI62xjPlpdwYDapD2aIBjcKbdgMeODSyc6hM0_IL8uO4u0vx3x7zbMeQPQ6DmzDus5XKlFGjC3h9BH2KOSfs7C6F0aVXC9QeNNqi0R40WpC2aCyNb6fp_WbE9p0_eSvA9xPgsndDlw6v53dOam3K5cJdHblt6Lf_Q0KbRzcMZZbZFx8Zt6AsNwr4GyVDhrY</recordid><startdate>20050610</startdate><enddate>20050610</enddate><creator>BHALLA, Kapil N</creator><general>American Society of Clinical Oncology</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20050610</creationdate><title>Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies</title><author>BHALLA, Kapil N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-458232720b34526233015a0d9c27c66b9817fe6de918e5c9db1c13146fae794d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Chromatin - genetics</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Silencing</topic><topic>Genetic Therapy</topic><topic>Histone Deacetylase Inhibitors</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Methyltransferases - metabolism</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - therapy</topic><topic>Promoter Regions, Genetic</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BHALLA, Kapil N</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BHALLA, Kapil N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2005-06-10</date><risdate>2005</risdate><volume>23</volume><issue>17</issue><spage>3971</spage><epage>3993</epage><pages>3971-3993</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>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. 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| ispartof | Journal of clinical oncology, 2005-06, Vol.23 (17), p.3971-3993 |
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| language | eng |
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| source | MEDLINE; American Society of Clinical Oncology; EZB Electronic Journals Library |
| subjects | Biological and medical sciences Chromatin - genetics DNA Methylation Epigenesis, Genetic Gene Expression Regulation, Neoplastic Gene Silencing Genetic Therapy Histone Deacetylase Inhibitors Humans Medical sciences Methyltransferases - metabolism Neoplasms - genetics Neoplasms - therapy Promoter Regions, Genetic Tumors |
| title | Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies |
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