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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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