Academic Journal
Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells
| العنوان: | Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells |
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| المؤلفون: | Kouzi, Farah, Zibara, Kazem, Bourgeais, Jerome, Picou, Frederic, Gallay, Nathalie, Brossaud, Julie, Dakik, Hassan, Roux, Benjamin, Hamard, Sophie, Le Nail, Louis-Romée, Hleihel, Rita, Foucault, Amelie, Ravalet, Noemie, Rouleux-Bonnin, Florence, Gouilleux, Fabrice, Mazurier, Frédéric, Béné, Marie, C, Akl, Haidar, Gyan, Emmanuel, Domenech, Jorge, El-Sabban, Marwan, Herault, Olivier |
| المساهمون: | Université de Tours (UT), الجامعة اللبنانية بيروت = Lebanese University Beirut = Université libanaise Beyrouth (LU / ULB), CHU Bordeaux, CHU Trousseau Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), American University of Beirut Beyrouth (AUB), Groupe innovation et ciblage cellulaire (GICC), EA 7501 2018-.2022 (GICC EA 7501), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN) |
| المصدر: | ISSN: 0950-9232. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | Université François-Rabelais de Tours: HAL |
| مصطلحات موضوعية: | Acute myeloid leukaemia, Cancer microenvironment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology |
| الوصف: | International audience ; The bone marrow (BM) niche impacts the progression of acute myeloid leukemia (AML) by favoring the chemoresistance of AML cells. Intimate interactions between leukemic cells and BM mesenchymal stromal cells (BM-MSCs) play key roles in this process. Direct intercellular communications between hematopoietic cells and BM-MSCs involve connexins, components of gap junctions. We postulated that blocking gap junction assembly could modify cell-cell interactions in the leukemic niche and consequently the chemoresistance. The comparison of BM-MSCs from AML patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presents an antileukemic effect without affecting normal BM-CD34 + progenitor cells. The proapoptotic effect of CBX on AML cells is in line with the extinction of energy metabolism. CBX acts synergistically with cytarabine (Ara-C) in vitro and in vivo. Coculture experiments of AML cells with BM-MSCs revealed that CBX neutralizes the protective effect of the niche against the Ara-C-induced apoptosis of leukemic cells. Altogether, these results suggest that CBX could be of therapeutic interest to reduce the chemoresistance favored by the leukemic niche, by targeting gap junctions, without affecting normal hematopoiesis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-02411718; https://univ-tours.hal.science/hal-02411718; https://univ-tours.hal.science/hal-02411718/document; https://univ-tours.hal.science/hal-02411718/file/s41388-019-1069-y.pdf |
| DOI: | 10.1038/s41388-019-1069-y |
| الاتاحة: | https://univ-tours.hal.science/hal-02411718 https://univ-tours.hal.science/hal-02411718/document https://univ-tours.hal.science/hal-02411718/file/s41388-019-1069-y.pdf https://doi.org/10.1038/s41388-019-1069-y |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.43016E48 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41388-019-1069-y |
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