Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.
Identifieur interne : 000890 ( PubMed/Checkpoint ); précédent : 000889; suivant : 000891Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.
Auteurs : Samantha L. Ginn [Australie] ; Claus V. Hallwirth [Australie] ; Sophia H Y. Liao [Australie] ; Erdahl T. Teber [Australie] ; Jonathan W. Arthur [Australie] ; Jianmin Wu [Australie] ; Hong Ching Lee [Australie] ; Szun S. Tay [Australie] ; Min Hu [Australie] ; Roger R. Reddel [Australie] ; Matthew P. Mccormack [Australie] ; Adrian J. Thrasher [Royaume-Uni] ; Marina Cavazzana [France] ; Stephen I. Alexander [Australie] ; Ian E. Alexander [Australie]Source :
- Molecular therapy. Nucleic acids [ 2162-2531 ] ; 2017.
Abstract
In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy. To test this hypothesis, in the absence of transduction, SCID-X1 mice were reconstituted with serially fewer wild-type hematopoietic progenitors. A robust inverse correlation between hematopoietic progenitor cell dose and T-lymphoid malignancy was observed, with earlier disease onset at lower cell doses. Malignancies were of donor origin and carried activating Notch1 mutations. These findings align with emerging evidence that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Although insertional proto-oncogene activation is required for the development of malignancy in humans, failure of γc-deficient thymocytes to effectively compete with this at-risk cell population may have also contributed to oncogenesis observed in early SCID-X1 trials.
DOI: 10.1016/j.omtn.2016.11.011
PubMed: 28325276
Affiliations:
- Australie, France, Royaume-Uni
- Nouvelle-Galles du Sud, Île-de-France
- Paris, Sydney
- Université de Sydney
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Ginn</name><affiliation wicri:level="1"><nlm:affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145</wicri:regionArea><wicri:noRegion>NSW 2145</wicri:noRegion></affiliation></author><author><name sortKey="Hallwirth, Claus V" sort="Hallwirth, Claus V" uniqKey="Hallwirth C" first="Claus V" last="Hallwirth">Claus V. Hallwirth</name><affiliation wicri:level="1"><nlm:affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145</wicri:regionArea><wicri:noRegion>NSW 2145</wicri:noRegion></affiliation></author><author><name sortKey="Liao, Sophia H Y" sort="Liao, Sophia H Y" uniqKey="Liao S" first="Sophia H Y" last="Liao">Sophia H Y. Liao</name><affiliation wicri:level="1"><nlm:affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145</wicri:regionArea><wicri:noRegion>NSW 2145</wicri:noRegion></affiliation></author><author><name sortKey="Teber, Erdahl T" sort="Teber, Erdahl T" uniqKey="Teber E" first="Erdahl T" last="Teber">Erdahl T. Teber</name><affiliation wicri:level="4"><nlm:affiliation>Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Arthur, Jonathan W" sort="Arthur, Jonathan W" uniqKey="Arthur J" first="Jonathan W" last="Arthur">Jonathan W. Arthur</name><affiliation wicri:level="4"><nlm:affiliation>Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Wu, Jianmin" sort="Wu, Jianmin" uniqKey="Wu J" first="Jianmin" last="Wu">Jianmin Wu</name><affiliation wicri:level="1"><nlm:affiliation>Kinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Kinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010</wicri:regionArea><wicri:noRegion>NSW 2010</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Hong Ching" sort="Lee, Hong Ching" uniqKey="Lee H" first="Hong Ching" last="Lee">Hong Ching Lee</name><affiliation wicri:level="1"><nlm:affiliation>Kinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Kinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010</wicri:regionArea><wicri:noRegion>NSW 2010</wicri:noRegion></affiliation></author><author><name sortKey="Tay, Szun S" sort="Tay, Szun S" uniqKey="Tay S" first="Szun S" last="Tay">Szun S. Tay</name><affiliation wicri:level="1"><nlm:affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145</wicri:regionArea><wicri:noRegion>NSW 2145</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Min" sort="Hu, Min" uniqKey="Hu M" first="Min" last="Hu">Min Hu</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145</wicri:regionArea><wicri:noRegion>NSW 2145</wicri:noRegion></affiliation></author><author><name sortKey="Reddel, Roger R" sort="Reddel, Roger R" uniqKey="Reddel R" first="Roger R" last="Reddel">Roger R. Reddel</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Mccormack, Matthew P" sort="Mccormack, Matthew P" uniqKey="Mccormack M" first="Matthew P" last="Mccormack">Matthew P. Mccormack</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3800</wicri:regionArea><wicri:noRegion>VIC 3800</wicri:noRegion></affiliation></author><author><name sortKey="Thrasher, Adrian J" sort="Thrasher, Adrian J" uniqKey="Thrasher A" first="Adrian J" last="Thrasher">Adrian J. Thrasher</name><affiliation wicri:level="1"><nlm:affiliation>Infection, Immunity, Inflammation, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Infection, Immunity, Inflammation, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH</wicri:regionArea><wicri:noRegion>London WC1N 1EH</wicri:noRegion></affiliation></author><author><name sortKey="Cavazzana, Marina" sort="Cavazzana, Marina" uniqKey="Cavazzana M" first="Marina" last="Cavazzana">Marina Cavazzana</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotherapy, Hôpital Necker-Enfants Malades, Paris 75015, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Biotherapy, Hôpital Necker-Enfants Malades, Paris 75015</wicri:regionArea><wicri:noRegion>75015</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Alexander, Stephen I" sort="Alexander, Stephen I" uniqKey="Alexander S" first="Stephen I" last="Alexander">Stephen I. Alexander</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Alexander, Ian E" sort="Alexander, Ian E" uniqKey="Alexander I" first="Ian E" last="Alexander">Ian E. Alexander</name><affiliation wicri:level="1"><nlm:affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia. Electronic address: ian.alexander@health.nsw.gov.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145</wicri:regionArea><wicri:noRegion>NSW 2145</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular therapy. Nucleic acids</title><idno type="ISSN">2162-2531</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">In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy. To test this hypothesis, in the absence of transduction, SCID-X1 mice were reconstituted with serially fewer wild-type hematopoietic progenitors. A robust inverse correlation between hematopoietic progenitor cell dose and T-lymphoid malignancy was observed, with earlier disease onset at lower cell doses. Malignancies were of donor origin and carried activating Notch1 mutations. These findings align with emerging evidence that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Although insertional proto-oncogene activation is required for the development of malignancy in humans, failure of γc-deficient thymocytes to effectively compete with this at-risk cell population may have also contributed to oncogenesis observed in early SCID-X1 trials.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">28325276</PMID><DateCreated><Year>2017</Year><Month>03</Month><Day>22</Day></DateCreated><DateRevised><Year>2017</Year><Month>08</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">2162-2531</ISSN><JournalIssue CitedMedium="Print"><Volume>6</Volume><PubDate><Year>2017</Year><Month>Mar</Month><Day>17</Day></PubDate></JournalIssue><Title>Molecular therapy. Nucleic acids</Title><ISOAbbreviation>Mol Ther Nucleic Acids</ISOAbbreviation></Journal><ArticleTitle>Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.</ArticleTitle><Pagination><MedlinePgn>1-14</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2162-2531(16)30370-5</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.omtn.2016.11.011</ELocationID><Abstract><AbstractText>In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy. To test this hypothesis, in the absence of transduction, SCID-X1 mice were reconstituted with serially fewer wild-type hematopoietic progenitors. A robust inverse correlation between hematopoietic progenitor cell dose and T-lymphoid malignancy was observed, with earlier disease onset at lower cell doses. Malignancies were of donor origin and carried activating Notch1 mutations. These findings align with emerging evidence that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Although insertional proto-oncogene activation is required for the development of malignancy in humans, failure of γc-deficient thymocytes to effectively compete with this at-risk cell population may have also contributed to oncogenesis observed in early SCID-X1 trials.</AbstractText><CopyrightInformation>Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ginn</LastName><ForeName>Samantha L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hallwirth</LastName><ForeName>Claus V</ForeName><Initials>CV</Initials><AffiliationInfo><Affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Sophia H Y</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Teber</LastName><ForeName>Erdahl T</ForeName><Initials>ET</Initials><AffiliationInfo><Affiliation>Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arthur</LastName><ForeName>Jonathan W</ForeName><Initials>JW</Initials><AffiliationInfo><Affiliation>Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Jianmin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Kinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Hong Ching</ForeName><Initials>HC</Initials><AffiliationInfo><Affiliation>Kinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tay</LastName><ForeName>Szun S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Min</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Centre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reddel</LastName><ForeName>Roger R</ForeName><Initials>RR</Initials><AffiliationInfo><Affiliation>Cancer Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McCormack</LastName><ForeName>Matthew P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3800, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thrasher</LastName><ForeName>Adrian J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Infection, Immunity, Inflammation, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cavazzana</LastName><ForeName>Marina</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biotherapy, Hôpital Necker-Enfants Malades, Paris 75015, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alexander</LastName><ForeName>Stephen I</ForeName><Initials>SI</Initials><AffiliationInfo><Affiliation>Centre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alexander</LastName><ForeName>Ian E</ForeName><Initials>IE</Initials><AffiliationInfo><Affiliation>Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia. 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PubStatus="received"><Year>2016</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>11</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>11</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28325276</ArticleId><ArticleId IdType="pii">S2162-2531(16)30370-5</ArticleId><ArticleId IdType="doi">10.1016/j.omtn.2016.11.011</ArticleId><ArticleId IdType="pmc">PMC5363493</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li></country><region><li>Nouvelle-Galles du Sud</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Sydney</li></settlement><orgName><li>Université de Sydney</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Ginn, Samantha L" sort="Ginn, Samantha L" uniqKey="Ginn S" first="Samantha L" last="Ginn">Samantha L. Ginn</name></noRegion><name sortKey="Alexander, Ian E" sort="Alexander, Ian E" uniqKey="Alexander I" first="Ian E" last="Alexander">Ian E. Alexander</name><name sortKey="Alexander, Stephen I" sort="Alexander, Stephen I" uniqKey="Alexander S" first="Stephen I" last="Alexander">Stephen I. Alexander</name><name sortKey="Arthur, Jonathan W" sort="Arthur, Jonathan W" uniqKey="Arthur J" first="Jonathan W" last="Arthur">Jonathan W. Arthur</name><name sortKey="Hallwirth, Claus V" sort="Hallwirth, Claus V" uniqKey="Hallwirth C" first="Claus V" last="Hallwirth">Claus V. Hallwirth</name><name sortKey="Hu, Min" sort="Hu, Min" uniqKey="Hu M" first="Min" last="Hu">Min Hu</name><name sortKey="Lee, Hong Ching" sort="Lee, Hong Ching" uniqKey="Lee H" first="Hong Ching" last="Lee">Hong Ching Lee</name><name sortKey="Liao, Sophia H Y" sort="Liao, Sophia H Y" uniqKey="Liao S" first="Sophia H Y" last="Liao">Sophia H Y. Liao</name><name sortKey="Mccormack, Matthew P" sort="Mccormack, Matthew P" uniqKey="Mccormack M" first="Matthew P" last="Mccormack">Matthew P. Mccormack</name><name sortKey="Reddel, Roger R" sort="Reddel, Roger R" uniqKey="Reddel R" first="Roger R" last="Reddel">Roger R. Reddel</name><name sortKey="Tay, Szun S" sort="Tay, Szun S" uniqKey="Tay S" first="Szun S" last="Tay">Szun S. Tay</name><name sortKey="Teber, Erdahl T" sort="Teber, Erdahl T" uniqKey="Teber E" first="Erdahl T" last="Teber">Erdahl T. Teber</name><name sortKey="Wu, Jianmin" sort="Wu, Jianmin" uniqKey="Wu J" first="Jianmin" last="Wu">Jianmin Wu</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Thrasher, Adrian J" sort="Thrasher, Adrian J" uniqKey="Thrasher A" first="Adrian J" last="Thrasher">Adrian J. Thrasher</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Cavazzana, Marina" sort="Cavazzana, Marina" uniqKey="Cavazzana M" first="Marina" last="Cavazzana">Marina Cavazzana</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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