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A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports
The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695792/ https://www.ncbi.nlm.nih.gov/pubmed/34956909 http://dx.doi.org/10.3389/fonc.2021.797941 |
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author | Wang, Bin-Ru Wan, Chao-Ling Liu, Song-Bai Qiu, Qiao-Cheng Wu, Tian-Mei Wang, Jun Li, Yan-Yan Ge, Shuai-Shuai Qiu, Yan Shen, Xiang-Dong Xue, Sheng-Li Li, Zheng |
author_facet | Wang, Bin-Ru Wan, Chao-Ling Liu, Song-Bai Qiu, Qiao-Cheng Wu, Tian-Mei Wang, Jun Li, Yan-Yan Ge, Shuai-Shuai Qiu, Yan Shen, Xiang-Dong Xue, Sheng-Li Li, Zheng |
author_sort | Wang, Bin-Ru |
collection | PubMed |
description | The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful. |
format | Online Article Text |
id | pubmed-8695792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86957922021-12-24 A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports Wang, Bin-Ru Wan, Chao-Ling Liu, Song-Bai Qiu, Qiao-Cheng Wu, Tian-Mei Wang, Jun Li, Yan-Yan Ge, Shuai-Shuai Qiu, Yan Shen, Xiang-Dong Xue, Sheng-Li Li, Zheng Front Oncol Oncology The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful. Frontiers Media S.A. 2021-12-09 /pmc/articles/PMC8695792/ /pubmed/34956909 http://dx.doi.org/10.3389/fonc.2021.797941 Text en Copyright © 2021 Wang, Wan, Liu, Qiu, Wu, Wang, Li, Ge, Qiu, Shen, Xue and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Wang, Bin-Ru Wan, Chao-Ling Liu, Song-Bai Qiu, Qiao-Cheng Wu, Tian-Mei Wang, Jun Li, Yan-Yan Ge, Shuai-Shuai Qiu, Yan Shen, Xiang-Dong Xue, Sheng-Li Li, Zheng A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports |
title | A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports |
title_full | A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports |
title_fullStr | A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports |
title_full_unstemmed | A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports |
title_short | A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports |
title_sort | combined histone deacetylases targeting strategy to overcome venetoclax plus azacitidine regimen resistance in acute myeloid leukaemia: three case reports |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695792/ https://www.ncbi.nlm.nih.gov/pubmed/34956909 http://dx.doi.org/10.3389/fonc.2021.797941 |
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