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HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells
Since imatinib (Glivec or Gleevec) has been used to target the BCR-ABL fusion protein, chronic myeloid leukemia (CML) has become a manageable chronic disease with long-term survival. However, 15%–20% of CML patients ultimately develop resistance to imatinib and then progress to an accelerated phase...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539538/ https://www.ncbi.nlm.nih.gov/pubmed/31071955 http://dx.doi.org/10.3390/ijms20092271 |
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author | Chen, Shu-Huey Chow, Jyh-Ming Hsieh, Yao-Yu Lin, Chun-Yu Hsu, Kai-Wen Hsieh, Wen-Shyang Chi, Wei-Ming Shabangu, Beished M. Lee, Chia-Hwa |
author_facet | Chen, Shu-Huey Chow, Jyh-Ming Hsieh, Yao-Yu Lin, Chun-Yu Hsu, Kai-Wen Hsieh, Wen-Shyang Chi, Wei-Ming Shabangu, Beished M. Lee, Chia-Hwa |
author_sort | Chen, Shu-Huey |
collection | PubMed |
description | Since imatinib (Glivec or Gleevec) has been used to target the BCR-ABL fusion protein, chronic myeloid leukemia (CML) has become a manageable chronic disease with long-term survival. However, 15%–20% of CML patients ultimately develop resistance to imatinib and then progress to an accelerated phase and eventually to a blast crisis, limiting treatment options and resulting in a poor survival rate. Thus, we investigated whether histone deacetylase inhibitors (HDACis) could be used as a potential anticancer therapy for imatinib-resistant CML (IR-CML) patients. By applying a noninvasive apoptosis detection sensor (NIADS), we found that panobinostat significantly enhanced cell apoptosis in K562 cells. A further investigation showed that panobinostat induced apoptosis in both K562 and imatinib-resistant K562 (IR-K562) cells mainly via H3 and H4 histone acetylation, whereas panobinostat targeted cancer stem cells (CSCs) in IR-K562 cells. Using CRISPR/Cas9 genomic editing, we found that HDAC1 and HDAC2 knockout cells significantly induced cell apoptosis, indicating that the regulation of HDAC1 and HDAC2 is extremely important in maintaining K562 cell survival. All information in this study indicates that regulating HDAC activity provides therapeutic benefits against CML and IR-CML in the clinic. |
format | Online Article Text |
id | pubmed-6539538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65395382019-06-04 HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells Chen, Shu-Huey Chow, Jyh-Ming Hsieh, Yao-Yu Lin, Chun-Yu Hsu, Kai-Wen Hsieh, Wen-Shyang Chi, Wei-Ming Shabangu, Beished M. Lee, Chia-Hwa Int J Mol Sci Article Since imatinib (Glivec or Gleevec) has been used to target the BCR-ABL fusion protein, chronic myeloid leukemia (CML) has become a manageable chronic disease with long-term survival. However, 15%–20% of CML patients ultimately develop resistance to imatinib and then progress to an accelerated phase and eventually to a blast crisis, limiting treatment options and resulting in a poor survival rate. Thus, we investigated whether histone deacetylase inhibitors (HDACis) could be used as a potential anticancer therapy for imatinib-resistant CML (IR-CML) patients. By applying a noninvasive apoptosis detection sensor (NIADS), we found that panobinostat significantly enhanced cell apoptosis in K562 cells. A further investigation showed that panobinostat induced apoptosis in both K562 and imatinib-resistant K562 (IR-K562) cells mainly via H3 and H4 histone acetylation, whereas panobinostat targeted cancer stem cells (CSCs) in IR-K562 cells. Using CRISPR/Cas9 genomic editing, we found that HDAC1 and HDAC2 knockout cells significantly induced cell apoptosis, indicating that the regulation of HDAC1 and HDAC2 is extremely important in maintaining K562 cell survival. All information in this study indicates that regulating HDAC activity provides therapeutic benefits against CML and IR-CML in the clinic. MDPI 2019-05-08 /pmc/articles/PMC6539538/ /pubmed/31071955 http://dx.doi.org/10.3390/ijms20092271 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Shu-Huey Chow, Jyh-Ming Hsieh, Yao-Yu Lin, Chun-Yu Hsu, Kai-Wen Hsieh, Wen-Shyang Chi, Wei-Ming Shabangu, Beished M. Lee, Chia-Hwa HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells |
title | HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells |
title_full | HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells |
title_fullStr | HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells |
title_full_unstemmed | HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells |
title_short | HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells |
title_sort | hdac1,2 knock-out and hdaci induced cell apoptosis in imatinib-resistant k562 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539538/ https://www.ncbi.nlm.nih.gov/pubmed/31071955 http://dx.doi.org/10.3390/ijms20092271 |
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