High Throughput Fluorescence-Based In Vitro Experimental Platform for the Identification of Effective Therapies to Overcome Tumour Microenvironment-Mediated Drug Resistance in AML
dc.contributor.author | Arroyo Berdugo, Yoana | |
dc.contributor.author | Sendino Mouliet, Maria | |
dc.contributor.author | Greaves, David | |
dc.contributor.author | Nojszewska, Natalia | |
dc.contributor.author | Idilli, Orest | |
dc.contributor.author | So, Chi Wai | |
dc.contributor.author | Di Silvio, Lucy | |
dc.contributor.author | Quartey Papafio, Ruby | |
dc.contributor.author | Farzaneh, Farzin | |
dc.contributor.author | Rodríguez Pérez, José Antonio | |
dc.contributor.author | Calle, Yolanda | |
dc.date.accessioned | 2023-04-27T11:56:55Z | |
dc.date.available | 2023-04-27T11:56:55Z | |
dc.date.issued | 2023-03-27 | |
dc.identifier.citation | Cancers 15(7) : (2023) // Article ID 1988 | es_ES |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | http://hdl.handle.net/10810/60953 | |
dc.description.abstract | The interactions between Acute Myeloid Leukaemia (AML) leukemic stem cells and the bone marrow (BM) microenvironment play a critical role during AML progression and resistance to drug treatments. Therefore, the identification of novel therapies requires drug-screening methods using in vitro co-culture models that closely recreate the cytoprotective BM setting. We have developed a new fluorescence-based in vitro co-culture system scalable to high throughput for measuring the concomitant effect of drugs on AML cells and the cytoprotective BM microenvironment. eGFP-expressing AML cells are co-cultured in direct contact with mCherry-expressing BM stromal cells for the accurate assessment of proliferation, viability, and signaling in both cell types. This model identified several efficacious compounds that overcome BM stroma-mediated drug resistance against daunorubicin, including the chromosome region maintenance 1 (CRM1/XPO1) inhibitor KPT-330. In silico analysis of genes co-expressed with CRM1, combined with in vitro experiments using our new methodology, also indicates that the combination of KPT-330 with the AURKA pharmacological inhibitor alisertib circumvents the cytoprotection of AML cells mediated by the BM stroma. This new experimental model and analysis provide a more precise screening method for developing improved therapeutics targeting AML cells within the cytoprotective BM microenvironment. | es_ES |
dc.description.sponsorship | This research received funding from Cancer Research UK (reference C34579/A20784) and the Basque Country Government (reference IT1547-22). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | AML | es_ES |
dc.subject | tumour microenvironment | es_ES |
dc.subject | co-culture system | es_ES |
dc.subject | daunorubicin | es_ES |
dc.subject | resistance | es_ES |
dc.subject | KPT-330 | es_ES |
dc.subject | selinexor | es_ES |
dc.title | High Throughput Fluorescence-Based In Vitro Experimental Platform for the Identification of Effective Therapies to Overcome Tumour Microenvironment-Mediated Drug Resistance in AML | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2023-04-12T13:24:19Z | |
dc.rights.holder | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2072-6694/15/7/1988 | es_ES |
dc.identifier.doi | 10.3390/cancers15071988 | |
dc.departamentoes | Genética, antropología física y fisiología animal | |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia |
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).