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Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment
Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhib...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861361/ https://www.ncbi.nlm.nih.gov/pubmed/35211416 http://dx.doi.org/10.3389/fonc.2022.841276 |
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author | Li, Zheng Wang, Jun Ge, Shuai-Shuai Qiu, Qiao-Cheng Du, Jia-Hui Shan, Shuang-Shuang Shen, Xiang-Dong Wan, Chao-Ling Wang, Bin-Ru Wu, De-Pei Qiu, Hui-Ying Xue, Sheng-Li |
author_facet | Li, Zheng Wang, Jun Ge, Shuai-Shuai Qiu, Qiao-Cheng Du, Jia-Hui Shan, Shuang-Shuang Shen, Xiang-Dong Wan, Chao-Ling Wang, Bin-Ru Wu, De-Pei Qiu, Hui-Ying Xue, Sheng-Li |
author_sort | Li, Zheng |
collection | PubMed |
description | Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations. |
format | Online Article Text |
id | pubmed-8861361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88613612022-02-23 Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment Li, Zheng Wang, Jun Ge, Shuai-Shuai Qiu, Qiao-Cheng Du, Jia-Hui Shan, Shuang-Shuang Shen, Xiang-Dong Wan, Chao-Ling Wang, Bin-Ru Wu, De-Pei Qiu, Hui-Ying Xue, Sheng-Li Front Oncol Oncology Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations. Frontiers Media S.A. 2022-02-08 /pmc/articles/PMC8861361/ /pubmed/35211416 http://dx.doi.org/10.3389/fonc.2022.841276 Text en Copyright © 2022 Li, Wang, Ge, Qiu, Du, Shan, Shen, Wan, Wang, Wu, Qiu and Xue 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 Li, Zheng Wang, Jun Ge, Shuai-Shuai Qiu, Qiao-Cheng Du, Jia-Hui Shan, Shuang-Shuang Shen, Xiang-Dong Wan, Chao-Ling Wang, Bin-Ru Wu, De-Pei Qiu, Hui-Ying Xue, Sheng-Li Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment |
title | Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment |
title_full | Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment |
title_fullStr | Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment |
title_full_unstemmed | Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment |
title_short | Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment |
title_sort | combination of venetoclax and midostaurin efficiently suppressed relapsed t(8;21)acute myeloid leukemia with mutant kit after failure of venetoclax plus azacitidine treatment |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861361/ https://www.ncbi.nlm.nih.gov/pubmed/35211416 http://dx.doi.org/10.3389/fonc.2022.841276 |
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