A Microenvironment-Induced Myeloproliferative Syndrome Caused by RARγ Deficiency
Identifieur interne : 009036 ( Main/Exploration ); précédent : 009035; suivant : 009037A Microenvironment-Induced Myeloproliferative Syndrome Caused by RARγ Deficiency
Auteurs : Carl R. Walkley [Australie, États-Unis] ; Gemma Haines Olsen [Australie] ; Sebastian Dworkin [Australie] ; Stewart A. Fabb [Australie] ; Jeremy Swann [Australie] ; Grant A. Mcarthur [Australie] ; Susan V. Westmoreland [États-Unis] ; Pierre Chambon [France] ; David T. Scadden [États-Unis] ; Louise E. Purton [Australie, États-Unis]Source :
- Cell [ 0092-8674 ] ; 2007.
Abstract
Myeloproliferative syndromes (MPS) are largely considered to be intrinsic to hematopoietic cells. Here, we demonstrate that mice null for retinoic acid receptor gamma (RARγ), have an MPS that was induced solely by the RARγ deficient microenvironment. Eight week old RARγ-/- mice had significantly increased granulocyte/macrophage progenitors in bone marrow (BM), with elevated peripheral blood, BM and spleen granulocytes. The MPS phenotype continued for the lifespan of the mice and was more pronounced over time. Unexpectedly, transplant studies revealed this disease was not intrinsic to the hematopoietic cells. Wildtype BM transplanted into mice with an RARγ null microenvironment rapidly developed the MPS. Significantly elevated TNFα in RARγ-/- mice contributed to the MPS, but transplantation of TNFα-/- BM did not prevent the microenvironment-induced MPS. These data show that loss of RARγ results in a non-hematopoietic cell intrinsic MPS, revealing the capability of the microenvironment to be the sole cause of hematopoietic disorders.
Url:
DOI: 10.1016/j.cell.2007.05.014
PubMed: 17574023
PubMed Central: 1974882
Affiliations:
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Walkley</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A2">Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">Department of Pediatric Oncology and Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children’s Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatric Oncology and Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children’s Hospital, Harvard Medical School, Boston, Massachusetts, 02115</wicri:regionArea><wicri:noRegion>02115</wicri:noRegion></affiliation></author><author><name sortKey="Olsen, Gemma Haines" sort="Olsen, Gemma Haines" uniqKey="Olsen G" first="Gemma Haines" last="Olsen">Gemma Haines Olsen</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation></author><author><name sortKey="Dworkin, Sebastian" sort="Dworkin, Sebastian" uniqKey="Dworkin S" first="Sebastian" last="Dworkin">Sebastian Dworkin</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation></author><author><name sortKey="Fabb, Stewart A" sort="Fabb, Stewart A" uniqKey="Fabb S" first="Stewart A." last="Fabb">Stewart A. Fabb</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation></author><author><name sortKey="Swann, Jeremy" sort="Swann, Jeremy" uniqKey="Swann J" first="Jeremy" last="Swann">Jeremy Swann</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation></author><author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A2">Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Haematology and Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Haematology and Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation></author><author><name sortKey="Westmoreland, Susan V" sort="Westmoreland, Susan V" uniqKey="Westmoreland S" first="Susan V" last="Westmoreland">Susan V. Westmoreland</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114</wicri:regionArea><wicri:noRegion>02114</wicri:noRegion></affiliation></author><author><name sortKey="Chambon, Pierre" sort="Chambon, Pierre" uniqKey="Chambon P" first="Pierre" last="Chambon">Pierre Chambon</name><affiliation wicri:level="1"><nlm:aff id="A6">Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, 67404 Illkirch Cedex, CU de Strasbourg, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, 67404 Illkirch Cedex, CU de Strasbourg</wicri:regionArea><wicri:noRegion>CU de Strasbourg</wicri:noRegion><wicri:noRegion>CU de Strasbourg</wicri:noRegion></affiliation></author><author><name sortKey="Scadden, David T" sort="Scadden, David T" uniqKey="Scadden D" first="David T" last="Scadden">David T. Scadden</name><affiliation wicri:level="1"><nlm:aff id="A7">Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114</wicri:regionArea><wicri:noRegion>02114</wicri:noRegion></affiliation></author><author><name sortKey="Purton, Louise E" sort="Purton, Louise E" uniqKey="Purton L" first="Louise E." last="Purton">Louise E. Purton</name><affiliation wicri:level="1"><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A7">Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114</wicri:regionArea><wicri:noRegion>02114</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell</title><idno type="ISSN">0092-8674</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p id="P1">Myeloproliferative syndromes (MPS) are largely considered to be intrinsic to hematopoietic cells. Here, we demonstrate that mice null for retinoic acid receptor gamma (RARγ), have an MPS that was induced solely by the RARγ deficient microenvironment. Eight week old RARγ<sup>-/-</sup> mice had significantly increased granulocyte/macrophage progenitors in bone marrow (BM), with elevated peripheral blood, BM and spleen granulocytes. The MPS phenotype continued for the lifespan of the mice and was more pronounced over time. Unexpectedly, transplant studies revealed this disease was not intrinsic to the hematopoietic cells. Wildtype BM transplanted into mice with an RARγ null microenvironment rapidly developed the MPS. Significantly elevated TNFα in RARγ<sup>-/-</sup> mice contributed to the MPS, but transplantation of TNFα<sup>-/-</sup> BM did not prevent the microenvironment-induced MPS. These data show that loss of RARγ results in a non-hematopoietic cell intrinsic MPS, revealing the capability of the microenvironment to be the sole cause of hematopoietic disorders.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>États-Unis</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="Walkley, Carl R" sort="Walkley, Carl R" uniqKey="Walkley C" first="Carl R." last="Walkley">Carl R. Walkley</name></noRegion><name sortKey="Dworkin, Sebastian" sort="Dworkin, Sebastian" uniqKey="Dworkin S" first="Sebastian" last="Dworkin">Sebastian Dworkin</name><name sortKey="Fabb, Stewart A" sort="Fabb, Stewart A" uniqKey="Fabb S" first="Stewart A." last="Fabb">Stewart A. Fabb</name><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name><name sortKey="Olsen, Gemma Haines" sort="Olsen, Gemma Haines" uniqKey="Olsen G" first="Gemma Haines" last="Olsen">Gemma Haines Olsen</name><name sortKey="Purton, Louise E" sort="Purton, Louise E" uniqKey="Purton L" first="Louise E." last="Purton">Louise E. Purton</name><name sortKey="Swann, Jeremy" sort="Swann, Jeremy" uniqKey="Swann J" first="Jeremy" last="Swann">Jeremy Swann</name><name sortKey="Walkley, Carl R" sort="Walkley, Carl R" uniqKey="Walkley C" first="Carl R." last="Walkley">Carl R. Walkley</name></country><country name="États-Unis"><noRegion><name sortKey="Walkley, Carl R" sort="Walkley, Carl R" uniqKey="Walkley C" first="Carl R." last="Walkley">Carl R. Walkley</name></noRegion><name sortKey="Purton, Louise E" sort="Purton, Louise E" uniqKey="Purton L" first="Louise E." last="Purton">Louise E. Purton</name><name sortKey="Scadden, David T" sort="Scadden, David T" uniqKey="Scadden D" first="David T" last="Scadden">David T. Scadden</name><name sortKey="Westmoreland, Susan V" sort="Westmoreland, Susan V" uniqKey="Westmoreland S" first="Susan V" last="Westmoreland">Susan V. Westmoreland</name></country><country name="France"><noRegion><name sortKey="Chambon, Pierre" sort="Chambon, Pierre" uniqKey="Chambon P" first="Pierre" last="Chambon">Pierre Chambon</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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