AustralieFrV1, Main, Exploration, bibRecord, 00B140

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1

Identifieur interne : 00B140 ( Main/Exploration ); précédent : 00B139; suivant : 00B141

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1

Auteurs : S. Hacein-Bey-Abina [France] ; C. Von Kalle [France, Allemagne, États-Unis] ; M. Schmidt [Allemagne] ; M. P. Mccormack [Royaume-Uni] ; N. Wulffraat [Pays-Bas] ; P. Leboulch [États-Unis] ; A. Lim [France] ; C. S. Osborne [Guinée] ; R. Pawliuk [États-Unis] ; E. Morillon [France] ; R. Sorensen [France] ; A. Forster [Royaume-Uni] ; P. Fraser [Guinée] ; J. I. Cohen [États-Unis] ; G. De Saint Basile [France] ; I. Alexander [Australie] ; U. Wintergerst [Allemagne] ; T. Frebourg [France] ; A. Aurias [France] ; D. Stoppa-Lyonnet [France] ; S. Romana [France] ; I. Radford-Weiss [France] ; F. Gross [France] ; F. Valensi [France] ; E. Delabesse [France] ; E. Macintyre [France] ; F. Sigaux [France] ; J. Soulier [France] ; L. E. Leiva [États-Unis] ; M. Wissler [Allemagne] ; C. Prinz [Allemagne] ; T. H. Rabbitts [Royaume-Uni] ; F. Le Deist [France] ; A. Fischer [France] ; M. Cavazzana-Calvo [France]

Source :

Science : (Washington, D.C.) [ 0036-8075 ] ; 2003.

RBID : Pascal:03-0524773

Descripteurs français

Pascal (Inist)
- Immunodéficit combiné sévère, Caractère lié au sexe, Chromosome X, Thérapie génique, Traitement, Protooncogène, Gène onc cellulaire, Lymphocyte T, Multiplication cellulaire, Retroviridae, Transfert génétique, Transduction, Gène, Chaîne peptidique γ, Mutagenèse, Complication, Homme, Gène LMO2.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- C-Onc gene, Cell proliferation, Complication, Gamma-Peptide chain, Gene, Gene therapy, Genetic transfer, Human, Mutagenesis, Protooncogene, Retroviridae, Severe combined immunodeficiency, Sex linked character, T-Lymphocyte, Transduction, Treatment, X-Chromosome.

Abstract

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as γ chain (γc) deficiency] in 9 out of 10 patients by retrovirus-mediated γc gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with γδ+ or αβ+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LM02 proto-oncogene promoter, leading to aberrant transcription and expression of LM02. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LM02 gene promoter.

Affiliations:

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Le document en format XML

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<country>France</country>
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</affiliation>
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<author><name sortKey="Fischer, A" sort="Fischer, A" uniqKey="Fischer A" first="A." last="Fischer">A. Fischer</name>
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<country>France</country>
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<author><name sortKey="Cavazzana Calvo, M" sort="Cavazzana Calvo, M" uniqKey="Cavazzana Calvo M" first="M." last="Cavazzana-Calvo">M. Cavazzana-Calvo</name>
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<country>France</country>
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</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1</title>
<author><name sortKey="Hacein Bey Abina, S" sort="Hacein Bey Abina, S" uniqKey="Hacein Bey Abina S" first="S." last="Hacein-Bey-Abina">S. Hacein-Bey-Abina</name>
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<country>France</country>
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<author><name sortKey="Von Kalle, C" sort="Von Kalle, C" uniqKey="Von Kalle C" first="C." last="Von Kalle">C. Von Kalle</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</s1>
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<country>France</country>
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</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Freiburg</s1>
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<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Institute of Molecular Medicine and Cell Research, University of Freiburg</s1>
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<country>Allemagne</country>
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<settlement type="city">Fribourg-en-Brisgau</settlement>
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<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Children's Hospital Research Foundation</s1>
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<country>États-Unis</country>
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<author><name sortKey="Schmidt, M" sort="Schmidt, M" uniqKey="Schmidt M" first="M." last="Schmidt">M. Schmidt</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Freiburg</s1>
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<sZ>2 aut.</sZ>
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<country>Allemagne</country>
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<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Institute of Molecular Medicine and Cell Research, University of Freiburg</s1>
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<sZ>2 aut.</sZ>
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<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
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<author><name sortKey="Mccormack, M P" sort="Mccormack, M P" uniqKey="Mccormack M" first="M. P." last="Mccormack">M. P. Mccormack</name>
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<sZ>4 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>32 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
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</affiliation>
</author>
<author><name sortKey="Wulffraat, N" sort="Wulffraat, N" uniqKey="Wulffraat N" first="N." last="Wulffraat">N. Wulffraat</name>
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<country>Pays-Bas</country>
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<author><name sortKey="Leboulch, P" sort="Leboulch, P" uniqKey="Leboulch P" first="P." last="Leboulch">P. Leboulch</name>
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</inist:fA14>
<country>États-Unis</country>
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</affiliation>
</author>
<author><name sortKey="Lim, A" sort="Lim, A" uniqKey="Lim A" first="A." last="Lim">A. Lim</name>
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<sZ>7 aut.</sZ>
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<country>France</country>
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</affiliation>
</author>
<author><name sortKey="Osborne, C S" sort="Osborne, C S" uniqKey="Osborne C" first="C. S." last="Osborne">C. S. Osborne</name>
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<sZ>8 aut.</sZ>
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</inist:fA14>
<country>Guinée</country>
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</affiliation>
</author>
<author><name sortKey="Pawliuk, R" sort="Pawliuk, R" uniqKey="Pawliuk R" first="R." last="Pawliuk">R. Pawliuk</name>
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</author>
<author><name sortKey="Morillon, E" sort="Morillon, E" uniqKey="Morillon E" first="E." last="Morillon">E. Morillon</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</s1>
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<sZ>1 aut.</sZ>
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<sZ>23 aut.</sZ>
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<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</wicri:noRegion>
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</author>
<author><name sortKey="Sorensen, R" sort="Sorensen, R" uniqKey="Sorensen R" first="R." last="Sorensen">R. Sorensen</name>
<affiliation wicri:level="3"><inist:fA14 i1="11"><s1>INSERM Unit 434, Institut Curie</s1>
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<sZ>11 aut.</sZ>
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<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Forster, A" sort="Forster, A" uniqKey="Forster A" first="A." last="Forster">A. Forster</name>
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<sZ>4 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>32 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Cambridge CB2 2QH</wicri:noRegion>
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<author><name sortKey="Fraser, P" sort="Fraser, P" uniqKey="Fraser P" first="P." last="Fraser">P. Fraser</name>
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<s3>GIN</s3>
<sZ>8 aut.</sZ>
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</inist:fA14>
<country>Guinée</country>
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</affiliation>
</author>
<author><name sortKey="Cohen, J I" sort="Cohen, J I" uniqKey="Cohen J" first="J. I." last="Cohen">J. I. Cohen</name>
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<country>États-Unis</country>
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</affiliation>
</author>
<author><name sortKey="De Saint Basile, G" sort="De Saint Basile, G" uniqKey="De Saint Basile G" first="G." last="De Saint Basile">G. De Saint Basile</name>
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<sZ>15 aut.</sZ>
<sZ>33 aut.</sZ>
<sZ>34 aut.</sZ>
<sZ>35 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
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</author>
<author><name sortKey="Alexander, I" sort="Alexander, I" uniqKey="Alexander I" first="I." last="Alexander">I. Alexander</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>The Children's Hospital at Westmead</s1>
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<sZ>16 aut.</sZ>
</inist:fA14>
<country>Australie</country>
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</affiliation>
</author>
<author><name sortKey="Wintergerst, U" sort="Wintergerst, U" uniqKey="Wintergerst U" first="U." last="Wintergerst">U. Wintergerst</name>
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<sZ>17 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Frebourg, T" sort="Frebourg, T" uniqKey="Frebourg T" first="T." last="Frebourg">T. Frebourg</name>
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<sZ>18 aut.</sZ>
</inist:fA14>
<country>France</country>
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</author>
<author><name sortKey="Aurias, A" sort="Aurias, A" uniqKey="Aurias A" first="A." last="Aurias">A. Aurias</name>
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</inist:fA14>
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<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Stoppa Lyonnet, D" sort="Stoppa Lyonnet, D" uniqKey="Stoppa Lyonnet D" first="D." last="Stoppa-Lyonnet">D. Stoppa-Lyonnet</name>
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<sZ>20 aut.</sZ>
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</inist:fA14>
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<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
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<s3>FRA</s3>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Laboratoire de Cytogénétique, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Radford Weiss, I" sort="Radford Weiss, I" uniqKey="Radford Weiss I" first="I." last="Radford-Weiss">I. Radford-Weiss</name>
<affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Laboratoire de Cytogénétique, University Paris V</s1>
<s3>FRA</s3>
<sZ>21 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Laboratoire de Cytogénétique, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gross, F" sort="Gross, F" uniqKey="Gross F" first="F." last="Gross">F. Gross</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>23 aut.</sZ>
<sZ>35 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Valensi, F" sort="Valensi, F" uniqKey="Valensi F" first="F." last="Valensi">F. Valensi</name>
<affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Laboratoire Central d'Hématologie and CNRS Unité de Recherche Associée 1461, University Paris V</s1>
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<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Laboratoire Central d'Hématologie and CNRS Unité de Recherche Associée 1461, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Delabesse, E" sort="Delabesse, E" uniqKey="Delabesse E" first="E." last="Delabesse">E. Delabesse</name>
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<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Laboratoire Central d'Hématologie and CNRS Unité de Recherche Associée 1461, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Macintyre, E" sort="Macintyre, E" uniqKey="Macintyre E" first="E." last="Macintyre">E. Macintyre</name>
<affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Laboratoire Central d'Hématologie and CNRS Unité de Recherche Associée 1461, University Paris V</s1>
<s3>FRA</s3>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Laboratoire Central d'Hématologie and CNRS Unité de Recherche Associée 1461, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sigaux, F" sort="Sigaux, F" uniqKey="Sigaux F" first="F." last="Sigaux">F. Sigaux</name>
<affiliation wicri:level="3"><inist:fA14 i1="16"><s1>Department of Oncology Genetics, Institut Curie</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>20 aut.</sZ>
<sZ>27 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Soulier, J" sort="Soulier, J" uniqKey="Soulier J" first="J." last="Soulier">J. Soulier</name>
<affiliation wicri:level="3"><inist:fA14 i1="19"><s1>INSERM Unit 462, Hôpital Saint Louis</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>28 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leiva, L E" sort="Leiva, L E" uniqKey="Leiva L" first="L. E." last="Leiva">L. E. Leiva</name>
<affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Department of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital</s1>
<s2>New Orleans, LA 70112</s2>
<s3>USA</s3>
<sZ>29 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>New Orleans, LA 70112</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wissler, M" sort="Wissler, M" uniqKey="Wissler M" first="M." last="Wissler">M. Wissler</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Freiburg</s1>
<s2>Freiburg</s2>
<s3>DEU</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>30 aut.</sZ>
<sZ>31 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Institute of Molecular Medicine and Cell Research, University of Freiburg</s1>
<s2>Freiburg</s2>
<s3>DEU</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>30 aut.</sZ>
<sZ>31 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Prinz, C" sort="Prinz, C" uniqKey="Prinz C" first="C." last="Prinz">C. Prinz</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Freiburg</s1>
<s2>Freiburg</s2>
<s3>DEU</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>30 aut.</sZ>
<sZ>31 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Institute of Molecular Medicine and Cell Research, University of Freiburg</s1>
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<s3>DEU</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>30 aut.</sZ>
<sZ>31 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rabbitts, T H" sort="Rabbitts, T H" uniqKey="Rabbitts T" first="T. H." last="Rabbitts">T. H. Rabbitts</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Medical Research Council, Laboratory of Molecular Biology, Hills Road</s1>
<s2>Cambridge CB2 2QH</s2>
<s3>GBR</s3>
<sZ>4 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>32 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Cambridge CB2 2QH</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Le Deist, F" sort="Le Deist, F" uniqKey="Le Deist F" first="F." last="Le Deist">F. Le Deist</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INSERM Unit 429, University Paris V</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>33 aut.</sZ>
<sZ>34 aut.</sZ>
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</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>INSERM Unit 429, University Paris V</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fischer, A" sort="Fischer, A" uniqKey="Fischer A" first="A." last="Fischer">A. Fischer</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INSERM Unit 429, University Paris V</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>33 aut.</sZ>
<sZ>34 aut.</sZ>
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</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>INSERM Unit 429, University Paris V</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="21"><s1>Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker</s1>
<s2>75743 Paris</s2>
<s3>FRA</s3>
<sZ>34 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>75743 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cavazzana Calvo, M" sort="Cavazzana Calvo, M" uniqKey="Cavazzana Calvo M" first="M." last="Cavazzana-Calvo">M. Cavazzana-Calvo</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INSERM Unit 429, University Paris V</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>33 aut.</sZ>
<sZ>34 aut.</sZ>
<sZ>35 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>INSERM Unit 429, University Paris V</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>23 aut.</sZ>
<sZ>35 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>University Paris V</wicri:noRegion>
<wicri:noRegion>Department de Biotherapie Assistance Publique-Hopitaux de Paris, University Paris V</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Science : (Washington, D.C.)</title>
<title level="j" type="abbreviated">Science : (Wash. D.C.)</title>
<idno type="ISSN">0036-8075</idno>
<imprint><date when="2003">2003</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Science : (Washington, D.C.)</title>
<title level="j" type="abbreviated">Science : (Wash. D.C.)</title>
<idno type="ISSN">0036-8075</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>C-Onc gene</term>
<term>Cell proliferation</term>
<term>Complication</term>
<term>Gamma-Peptide chain</term>
<term>Gene</term>
<term>Gene therapy</term>
<term>Genetic transfer</term>
<term>Human</term>
<term>Mutagenesis</term>
<term>Protooncogene</term>
<term>Retroviridae</term>
<term>Severe combined immunodeficiency</term>
<term>Sex linked character</term>
<term>T-Lymphocyte</term>
<term>Transduction</term>
<term>Treatment</term>
<term>X-Chromosome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Immunodéficit combiné sévère</term>
<term>Caractère lié au sexe</term>
<term>Chromosome X</term>
<term>Thérapie génique</term>
<term>Traitement</term>
<term>Protooncogène</term>
<term>Gène onc cellulaire</term>
<term>Lymphocyte T</term>
<term>Multiplication cellulaire</term>
<term>Retroviridae</term>
<term>Transfert génétique</term>
<term>Transduction</term>
<term>Gène</term>
<term>Chaîne peptidique γ</term>
<term>Mutagenèse</term>
<term>Complication</term>
<term>Homme</term>
<term>Gène LMO2</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as γ chain (γc) deficiency] in 9 out of 10 patients by retrovirus-mediated γc gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with γδ+ or αβ+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LM02 proto-oncogene promoter, leading to aberrant transcription and expression of LM02. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LM02 gene promoter.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>Guinée</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Bade-Wurtemberg</li>
<li>Bavière</li>
<li>District de Fribourg-en-Brisgau</li>
<li>District de Haute-Bavière</li>
<li>Utrecht (province)</li>
<li>Île-de-France</li>
</region>
<settlement><li>Fribourg-en-Brisgau</li>
<li>Munich</li>
<li>Paris</li>
<li>Utrecht</li>
</settlement>
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<tree><country name="France"><noRegion><name sortKey="Hacein Bey Abina, S" sort="Hacein Bey Abina, S" uniqKey="Hacein Bey Abina S" first="S." last="Hacein-Bey-Abina">S. Hacein-Bey-Abina</name>
</noRegion>
<name sortKey="Aurias, A" sort="Aurias, A" uniqKey="Aurias A" first="A." last="Aurias">A. Aurias</name>
<name sortKey="Cavazzana Calvo, M" sort="Cavazzana Calvo, M" uniqKey="Cavazzana Calvo M" first="M." last="Cavazzana-Calvo">M. Cavazzana-Calvo</name>
<name sortKey="Cavazzana Calvo, M" sort="Cavazzana Calvo, M" uniqKey="Cavazzana Calvo M" first="M." last="Cavazzana-Calvo">M. Cavazzana-Calvo</name>
<name sortKey="De Saint Basile, G" sort="De Saint Basile, G" uniqKey="De Saint Basile G" first="G." last="De Saint Basile">G. De Saint Basile</name>
<name sortKey="Delabesse, E" sort="Delabesse, E" uniqKey="Delabesse E" first="E." last="Delabesse">E. Delabesse</name>
<name sortKey="Fischer, A" sort="Fischer, A" uniqKey="Fischer A" first="A." last="Fischer">A. Fischer</name>
<name sortKey="Fischer, A" sort="Fischer, A" uniqKey="Fischer A" first="A." last="Fischer">A. Fischer</name>
<name sortKey="Frebourg, T" sort="Frebourg, T" uniqKey="Frebourg T" first="T." last="Frebourg">T. Frebourg</name>
<name sortKey="Gross, F" sort="Gross, F" uniqKey="Gross F" first="F." last="Gross">F. Gross</name>
<name sortKey="Hacein Bey Abina, S" sort="Hacein Bey Abina, S" uniqKey="Hacein Bey Abina S" first="S." last="Hacein-Bey-Abina">S. Hacein-Bey-Abina</name>
<name sortKey="Le Deist, F" sort="Le Deist, F" uniqKey="Le Deist F" first="F." last="Le Deist">F. Le Deist</name>
<name sortKey="Lim, A" sort="Lim, A" uniqKey="Lim A" first="A." last="Lim">A. Lim</name>
<name sortKey="Macintyre, E" sort="Macintyre, E" uniqKey="Macintyre E" first="E." last="Macintyre">E. Macintyre</name>
<name sortKey="Morillon, E" sort="Morillon, E" uniqKey="Morillon E" first="E." last="Morillon">E. Morillon</name>
<name sortKey="Radford Weiss, I" sort="Radford Weiss, I" uniqKey="Radford Weiss I" first="I." last="Radford-Weiss">I. Radford-Weiss</name>
<name sortKey="Romana, S" sort="Romana, S" uniqKey="Romana S" first="S." last="Romana">S. Romana</name>
<name sortKey="Sigaux, F" sort="Sigaux, F" uniqKey="Sigaux F" first="F." last="Sigaux">F. Sigaux</name>
<name sortKey="Sorensen, R" sort="Sorensen, R" uniqKey="Sorensen R" first="R." last="Sorensen">R. Sorensen</name>
<name sortKey="Soulier, J" sort="Soulier, J" uniqKey="Soulier J" first="J." last="Soulier">J. Soulier</name>
<name sortKey="Stoppa Lyonnet, D" sort="Stoppa Lyonnet, D" uniqKey="Stoppa Lyonnet D" first="D." last="Stoppa-Lyonnet">D. Stoppa-Lyonnet</name>
<name sortKey="Valensi, F" sort="Valensi, F" uniqKey="Valensi F" first="F." last="Valensi">F. Valensi</name>
<name sortKey="Von Kalle, C" sort="Von Kalle, C" uniqKey="Von Kalle C" first="C." last="Von Kalle">C. Von Kalle</name>
</country>
<country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Von Kalle, C" sort="Von Kalle, C" uniqKey="Von Kalle C" first="C." last="Von Kalle">C. Von Kalle</name>
</region>
<name sortKey="Prinz, C" sort="Prinz, C" uniqKey="Prinz C" first="C." last="Prinz">C. Prinz</name>
<name sortKey="Prinz, C" sort="Prinz, C" uniqKey="Prinz C" first="C." last="Prinz">C. Prinz</name>
<name sortKey="Schmidt, M" sort="Schmidt, M" uniqKey="Schmidt M" first="M." last="Schmidt">M. Schmidt</name>
<name sortKey="Schmidt, M" sort="Schmidt, M" uniqKey="Schmidt M" first="M." last="Schmidt">M. Schmidt</name>
<name sortKey="Von Kalle, C" sort="Von Kalle, C" uniqKey="Von Kalle C" first="C." last="Von Kalle">C. Von Kalle</name>
<name sortKey="Wintergerst, U" sort="Wintergerst, U" uniqKey="Wintergerst U" first="U." last="Wintergerst">U. Wintergerst</name>
<name sortKey="Wissler, M" sort="Wissler, M" uniqKey="Wissler M" first="M." last="Wissler">M. Wissler</name>
<name sortKey="Wissler, M" sort="Wissler, M" uniqKey="Wissler M" first="M." last="Wissler">M. Wissler</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Von Kalle, C" sort="Von Kalle, C" uniqKey="Von Kalle C" first="C." last="Von Kalle">C. Von Kalle</name>
</noRegion>
<name sortKey="Cohen, J I" sort="Cohen, J I" uniqKey="Cohen J" first="J. I." last="Cohen">J. I. Cohen</name>
<name sortKey="Leboulch, P" sort="Leboulch, P" uniqKey="Leboulch P" first="P." last="Leboulch">P. Leboulch</name>
<name sortKey="Leiva, L E" sort="Leiva, L E" uniqKey="Leiva L" first="L. E." last="Leiva">L. E. Leiva</name>
<name sortKey="Pawliuk, R" sort="Pawliuk, R" uniqKey="Pawliuk R" first="R." last="Pawliuk">R. Pawliuk</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Mccormack, M P" sort="Mccormack, M P" uniqKey="Mccormack M" first="M. P." last="Mccormack">M. P. Mccormack</name>
</noRegion>
<name sortKey="Forster, A" sort="Forster, A" uniqKey="Forster A" first="A." last="Forster">A. Forster</name>
<name sortKey="Rabbitts, T H" sort="Rabbitts, T H" uniqKey="Rabbitts T" first="T. H." last="Rabbitts">T. H. Rabbitts</name>
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   |wiki=    Wicri/Asie
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   |clé=     Pascal:03-0524773
   |texte=   LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
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	Serveur d'exploration sur les relations entre la France et l'Australie
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Serveur d'exploration sur les relations entre la France et l'Australie

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1

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