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Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML)
Aberrant epigenetic events contribute to tumorigenesis of all human cancers. Significant efforts are underway in developing new generation of epigenetic cancer therapeutics. Although clinical trials for agents targeting DNA hypermethylation and histone deacetylation have yielded promising results, d...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415792/ https://www.ncbi.nlm.nih.gov/pubmed/25928216 http://dx.doi.org/10.1371/journal.pone.0122983 |
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author | Jiang, Xia Lim, Cheryl Zi Hui Li, Zhimei Lee, Puay Leng Yatim, Siti Maryam J. M. Guan, Peiyong Li, Juntao Zhou, Jianbiao Pan, Jingxuan Chng, Wee-Joo Chai, Christina L. L. Yu, Qiang |
author_facet | Jiang, Xia Lim, Cheryl Zi Hui Li, Zhimei Lee, Puay Leng Yatim, Siti Maryam J. M. Guan, Peiyong Li, Juntao Zhou, Jianbiao Pan, Jingxuan Chng, Wee-Joo Chai, Christina L. L. Yu, Qiang |
author_sort | Jiang, Xia |
collection | PubMed |
description | Aberrant epigenetic events contribute to tumorigenesis of all human cancers. Significant efforts are underway in developing new generation of epigenetic cancer therapeutics. Although clinical trials for agents targeting DNA hypermethylation and histone deacetylation have yielded promising results, developing agents that target histone methylation remains to be in the early stage. We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range of anticancer effects in various human cancers. Here, focusing on acute myeloid leukemia (AML) as a model, we reported a less toxic analog of DZNep, named D9, which is shown to be efficacious in AML cell lines and patient-derived samples in vitro, as well as AML tumorigenesis in vivo. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy. |
format | Online Article Text |
id | pubmed-4415792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44157922015-05-07 Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) Jiang, Xia Lim, Cheryl Zi Hui Li, Zhimei Lee, Puay Leng Yatim, Siti Maryam J. M. Guan, Peiyong Li, Juntao Zhou, Jianbiao Pan, Jingxuan Chng, Wee-Joo Chai, Christina L. L. Yu, Qiang PLoS One Research Article Aberrant epigenetic events contribute to tumorigenesis of all human cancers. Significant efforts are underway in developing new generation of epigenetic cancer therapeutics. Although clinical trials for agents targeting DNA hypermethylation and histone deacetylation have yielded promising results, developing agents that target histone methylation remains to be in the early stage. We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range of anticancer effects in various human cancers. Here, focusing on acute myeloid leukemia (AML) as a model, we reported a less toxic analog of DZNep, named D9, which is shown to be efficacious in AML cell lines and patient-derived samples in vitro, as well as AML tumorigenesis in vivo. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy. Public Library of Science 2015-04-30 /pmc/articles/PMC4415792/ /pubmed/25928216 http://dx.doi.org/10.1371/journal.pone.0122983 Text en © 2015 Jiang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Jiang, Xia Lim, Cheryl Zi Hui Li, Zhimei Lee, Puay Leng Yatim, Siti Maryam J. M. Guan, Peiyong Li, Juntao Zhou, Jianbiao Pan, Jingxuan Chng, Wee-Joo Chai, Christina L. L. Yu, Qiang Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) |
title | Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) |
title_full | Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) |
title_fullStr | Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) |
title_full_unstemmed | Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) |
title_short | Functional Characterization of D9, a Novel Deazaneplanocin A (DZNep) Analog, in Targeting Acute Myeloid Leukemia (AML) |
title_sort | functional characterization of d9, a novel deazaneplanocin a (dznep) analog, in targeting acute myeloid leukemia (aml) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415792/ https://www.ncbi.nlm.nih.gov/pubmed/25928216 http://dx.doi.org/10.1371/journal.pone.0122983 |
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