Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer.
Identifieur interne : 000319 ( Main/Exploration ); précédent : 000318; suivant : 000320Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer.
Auteurs : Delphine Merino [Australie] ; James R. Whittle [Australie] ; François Vaillant [Australie] ; Antonin Serrano [Australie] ; Jia-Nan Gong [Australie] ; Goknur Giner [Australie] ; Ana Leticia Maragno [France] ; Maïa Chanrion [France] ; Emilie Schneider [France] ; Bhupinder Pal [Australie] ; Xiang Li [Australie] ; Grant Dewson [Australie] ; Julius Gr Sel [Australie] ; Kevin Liu [Australie] ; Najoua Lalaoui [Australie] ; David Segal [Australie] ; Marco J. Herold [Australie] ; David C S. Huang [Australie] ; Gordon K. Smyth [Australie] ; Olivier Geneste [France] ; Guillaume Lessene [Australie] ; Jane E. Visvader [Australie] ; Geoffrey J. Lindeman [Australie]Source :
- Science translational medicine [ 1946-6242 ] ; 2017.
Abstract
The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer. Using S63845-resistant cells combined with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) technology, we identified deletion of BAK and up-regulation of prosurvival proteins as potential mechanisms that confer resistance to S63845 in breast cancer. Collectively, our findings provide a strong rationale for the clinical evaluation of MCL-1 inhibitors in breast cancer.
DOI: 10.1126/scitranslmed.aam7049
PubMed: 28768804
Affiliations:
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sortKey="Herold, Marco J" sort="Herold, Marco J" uniqKey="Herold M" first="Marco J" last="Herold">Marco J. Herold</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Huang, David C S" sort="Huang, David C S" uniqKey="Huang D" first="David C S" last="Huang">David C S. Huang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Smyth, Gordon K" sort="Smyth, Gordon K" uniqKey="Smyth G" first="Gordon K" last="Smyth">Gordon K. Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Geneste, Olivier" sort="Geneste, Olivier" uniqKey="Geneste O" first="Olivier" last="Geneste">Olivier Geneste</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290</wicri:regionArea><wicri:noRegion>78290</wicri:noRegion><wicri:noRegion>78290</wicri:noRegion></affiliation></author><author><name sortKey="Lessene, Guillaume" sort="Lessene, Guillaume" uniqKey="Lessene G" first="Guillaume" last="Lessene">Guillaume Lessene</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Visvader, Jane E" sort="Visvader, Jane E" uniqKey="Visvader J" first="Jane E" last="Visvader">Jane E. Visvader</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. visvader@wehi.edu.au lindeman@wehi.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Lindeman, Geoffrey J" sort="Lindeman, Geoffrey J" uniqKey="Lindeman G" first="Geoffrey J" last="Lindeman">Geoffrey J. 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Whittle</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Vaillant, Francois" sort="Vaillant, Francois" uniqKey="Vaillant F" first="François" last="Vaillant">François Vaillant</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Serrano, Antonin" sort="Serrano, Antonin" uniqKey="Serrano A" first="Antonin" last="Serrano">Antonin Serrano</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Gong, Jia Nan" sort="Gong, Jia Nan" uniqKey="Gong J" first="Jia-Nan" last="Gong">Jia-Nan Gong</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Giner, Goknur" sort="Giner, Goknur" uniqKey="Giner G" first="Goknur" last="Giner">Goknur Giner</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Maragno, Ana Leticia" sort="Maragno, Ana Leticia" uniqKey="Maragno A" first="Ana Leticia" last="Maragno">Ana Leticia Maragno</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290</wicri:regionArea><wicri:noRegion>78290</wicri:noRegion><wicri:noRegion>78290</wicri:noRegion></affiliation></author><author><name sortKey="Chanrion, Maia" sort="Chanrion, Maia" uniqKey="Chanrion M" first="Maïa" last="Chanrion">Maïa Chanrion</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290</wicri:regionArea><wicri:noRegion>78290</wicri:noRegion><wicri:noRegion>78290</wicri:noRegion></affiliation></author><author><name sortKey="Schneider, Emilie" sort="Schneider, Emilie" uniqKey="Schneider E" first="Emilie" last="Schneider">Emilie Schneider</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290</wicri:regionArea><wicri:noRegion>78290</wicri:noRegion><wicri:noRegion>78290</wicri:noRegion></affiliation></author><author><name sortKey="Pal, Bhupinder" sort="Pal, Bhupinder" uniqKey="Pal B" first="Bhupinder" last="Pal">Bhupinder Pal</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Li, Xiang" sort="Li, Xiang" uniqKey="Li X" first="Xiang" last="Li">Xiang Li</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Dewson, Grant" sort="Dewson, Grant" uniqKey="Dewson G" first="Grant" last="Dewson">Grant Dewson</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Gr Sel, Julius" sort="Gr Sel, Julius" uniqKey="Gr Sel J" first="Julius" last="Gr Sel">Julius Gr Sel</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Kevin" sort="Liu, Kevin" uniqKey="Liu K" first="Kevin" last="Liu">Kevin Liu</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Lalaoui, Najoua" sort="Lalaoui, Najoua" uniqKey="Lalaoui N" first="Najoua" last="Lalaoui">Najoua Lalaoui</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Segal, David" sort="Segal, David" uniqKey="Segal D" first="David" last="Segal">David Segal</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Herold, Marco J" sort="Herold, Marco J" uniqKey="Herold M" first="Marco J" last="Herold">Marco J. Herold</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Huang, David C S" sort="Huang, David C S" uniqKey="Huang D" first="David C S" last="Huang">David C S. Huang</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Smyth, Gordon K" sort="Smyth, Gordon K" uniqKey="Smyth G" first="Gordon K" last="Smyth">Gordon K. Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Geneste, Olivier" sort="Geneste, Olivier" uniqKey="Geneste O" first="Olivier" last="Geneste">Olivier Geneste</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290</wicri:regionArea><wicri:noRegion>78290</wicri:noRegion><wicri:noRegion>78290</wicri:noRegion></affiliation></author><author><name sortKey="Lessene, Guillaume" sort="Lessene, Guillaume" uniqKey="Lessene G" first="Guillaume" last="Lessene">Guillaume Lessene</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Visvader, Jane E" sort="Visvader, Jane E" uniqKey="Visvader J" first="Jane E" last="Visvader">Jane E. Visvader</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. visvader@wehi.edu.au lindeman@wehi.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Lindeman, Geoffrey J" sort="Lindeman, Geoffrey J" uniqKey="Lindeman G" first="Geoffrey J" last="Lindeman">Geoffrey J. Lindeman</name><affiliation wicri:level="1"><nlm:affiliation>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. visvader@wehi.edu.au lindeman@wehi.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer. Using S63845-resistant cells combined with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) technology, we identified deletion of BAK and up-regulation of prosurvival proteins as potential mechanisms that confer resistance to S63845 in breast cancer. Collectively, our findings provide a strong rationale for the clinical evaluation of MCL-1 inhibitors in breast cancer.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Victoria (État)</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Merino, Delphine" sort="Merino, Delphine" uniqKey="Merino D" first="Delphine" last="Merino">Delphine Merino</name></noRegion><name sortKey="Dewson, Grant" sort="Dewson, Grant" uniqKey="Dewson G" first="Grant" last="Dewson">Grant Dewson</name><name sortKey="Giner, Goknur" sort="Giner, Goknur" uniqKey="Giner G" first="Goknur" last="Giner">Goknur Giner</name><name sortKey="Gong, Jia Nan" sort="Gong, Jia Nan" uniqKey="Gong J" first="Jia-Nan" last="Gong">Jia-Nan Gong</name><name sortKey="Gr Sel, Julius" sort="Gr Sel, Julius" uniqKey="Gr Sel J" first="Julius" last="Gr Sel">Julius Gr Sel</name><name sortKey="Herold, Marco J" sort="Herold, Marco J" uniqKey="Herold M" first="Marco J" last="Herold">Marco J. Herold</name><name sortKey="Huang, David C S" sort="Huang, David C S" uniqKey="Huang D" first="David C S" last="Huang">David C S. Huang</name><name sortKey="Lalaoui, Najoua" sort="Lalaoui, Najoua" uniqKey="Lalaoui N" first="Najoua" last="Lalaoui">Najoua Lalaoui</name><name sortKey="Lessene, Guillaume" sort="Lessene, Guillaume" uniqKey="Lessene G" first="Guillaume" last="Lessene">Guillaume Lessene</name><name sortKey="Li, Xiang" sort="Li, Xiang" uniqKey="Li X" first="Xiang" last="Li">Xiang Li</name><name sortKey="Lindeman, Geoffrey J" sort="Lindeman, Geoffrey J" uniqKey="Lindeman G" first="Geoffrey J" last="Lindeman">Geoffrey J. Lindeman</name><name sortKey="Liu, Kevin" sort="Liu, Kevin" uniqKey="Liu K" first="Kevin" last="Liu">Kevin Liu</name><name sortKey="Pal, Bhupinder" sort="Pal, Bhupinder" uniqKey="Pal B" first="Bhupinder" last="Pal">Bhupinder Pal</name><name sortKey="Segal, David" sort="Segal, David" uniqKey="Segal D" first="David" last="Segal">David Segal</name><name sortKey="Serrano, Antonin" sort="Serrano, Antonin" uniqKey="Serrano A" first="Antonin" last="Serrano">Antonin Serrano</name><name sortKey="Smyth, Gordon K" sort="Smyth, Gordon K" uniqKey="Smyth G" first="Gordon K" last="Smyth">Gordon K. Smyth</name><name sortKey="Vaillant, Francois" sort="Vaillant, Francois" uniqKey="Vaillant F" first="François" last="Vaillant">François Vaillant</name><name sortKey="Visvader, Jane E" sort="Visvader, Jane E" uniqKey="Visvader J" first="Jane E" last="Visvader">Jane E. Visvader</name><name sortKey="Whittle, James R" sort="Whittle, James R" uniqKey="Whittle J" first="James R" last="Whittle">James R. Whittle</name></country><country name="France"><noRegion><name sortKey="Maragno, Ana Leticia" sort="Maragno, Ana Leticia" uniqKey="Maragno A" first="Ana Leticia" last="Maragno">Ana Leticia Maragno</name></noRegion><name sortKey="Chanrion, Maia" sort="Chanrion, Maia" uniqKey="Chanrion M" first="Maïa" last="Chanrion">Maïa Chanrion</name><name sortKey="Geneste, Olivier" sort="Geneste, Olivier" uniqKey="Geneste O" first="Olivier" last="Geneste">Olivier Geneste</name><name sortKey="Schneider, Emilie" sort="Schneider, Emilie" uniqKey="Schneider E" first="Emilie" last="Schneider">Emilie Schneider</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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