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Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia
Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of Philadelphia chromosome‐positive acute lymphoblastic leukaemia (Ph(+) ALL), one of the most common and aggressive forms of haematological malignancies. However, TKI resistance has remained an unsolved issue. In this study...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824394/ https://www.ncbi.nlm.nih.gov/pubmed/29266867 http://dx.doi.org/10.1111/jcmm.13436 |
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author | Wang, Tao Cheng, Chunyan Peng, Lijun Gao, Mengqing Xi, Mengping Rousseaux, Sophie Khochbin, Saadi Wang, Jin Mi, Jianqing |
author_facet | Wang, Tao Cheng, Chunyan Peng, Lijun Gao, Mengqing Xi, Mengping Rousseaux, Sophie Khochbin, Saadi Wang, Jin Mi, Jianqing |
author_sort | Wang, Tao |
collection | PubMed |
description | Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of Philadelphia chromosome‐positive acute lymphoblastic leukaemia (Ph(+) ALL), one of the most common and aggressive forms of haematological malignancies. However, TKI resistance has remained an unsolved issue. In this study, we investigate the impact of adding arsenic trioxide (ATO) on the action of Dasatinib, a second‐generation TKI, in Ph(+) ALL. We show that ATO cooperates with Dasatinib in both TKI‐sensitive and resistant Ph(+) ALL cell lines to increase apoptosis and we unravel the underlying mechanisms. Indeed, combining ATO and Dasatinib leads to severe cell apoptosis by activating the UPR apoptotic IRE1/JNK/PUMA axis, while neutralizing the UPR ATF4‐dependent anti‐apoptotic axis, activated by ATO alone. Additionally, ATO and Dasatinib in combination repress the expression of several genes, which we previously showed to be associated with shorter survival probability in ALL patients. Overall these data support the use of ATO in combination with Dasatinib as a novel therapeutic regimen for Ph(+) ALL patients. |
format | Online Article Text |
id | pubmed-5824394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58243942018-03-01 Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia Wang, Tao Cheng, Chunyan Peng, Lijun Gao, Mengqing Xi, Mengping Rousseaux, Sophie Khochbin, Saadi Wang, Jin Mi, Jianqing J Cell Mol Med Original Articles Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of Philadelphia chromosome‐positive acute lymphoblastic leukaemia (Ph(+) ALL), one of the most common and aggressive forms of haematological malignancies. However, TKI resistance has remained an unsolved issue. In this study, we investigate the impact of adding arsenic trioxide (ATO) on the action of Dasatinib, a second‐generation TKI, in Ph(+) ALL. We show that ATO cooperates with Dasatinib in both TKI‐sensitive and resistant Ph(+) ALL cell lines to increase apoptosis and we unravel the underlying mechanisms. Indeed, combining ATO and Dasatinib leads to severe cell apoptosis by activating the UPR apoptotic IRE1/JNK/PUMA axis, while neutralizing the UPR ATF4‐dependent anti‐apoptotic axis, activated by ATO alone. Additionally, ATO and Dasatinib in combination repress the expression of several genes, which we previously showed to be associated with shorter survival probability in ALL patients. Overall these data support the use of ATO in combination with Dasatinib as a novel therapeutic regimen for Ph(+) ALL patients. John Wiley and Sons Inc. 2017-12-20 2018-03 /pmc/articles/PMC5824394/ /pubmed/29266867 http://dx.doi.org/10.1111/jcmm.13436 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wang, Tao Cheng, Chunyan Peng, Lijun Gao, Mengqing Xi, Mengping Rousseaux, Sophie Khochbin, Saadi Wang, Jin Mi, Jianqing Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia |
title | Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia |
title_full | Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia |
title_fullStr | Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia |
title_full_unstemmed | Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia |
title_short | Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome‐positive acute lymphoblastic leukaemia |
title_sort | combination of arsenic trioxide and dasatinib: a new strategy to treat philadelphia chromosome‐positive acute lymphoblastic leukaemia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824394/ https://www.ncbi.nlm.nih.gov/pubmed/29266867 http://dx.doi.org/10.1111/jcmm.13436 |
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