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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Microenvironment-Induced Myeloproliferative Syndrome Caused by RARγ Deficiency</title><author><name sortKey="Walkley, Carl R" sort="Walkley, Carl R" uniqKey="Walkley C" first="Carl R." last="Walkley">Carl R. Walkley</name><affiliation><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</nlm:aff></affiliation><affiliation><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></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation></author><author><name sortKey="Dworkin, Sebastian" sort="Dworkin, Sebastian" uniqKey="Dworkin S" first="Sebastian" last="Dworkin">Sebastian Dworkin</name><affiliation><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation></author><author><name sortKey="Swann, Jeremy" sort="Swann, Jeremy" uniqKey="Swann J" first="Jeremy" last="Swann">Jeremy Swann</name><affiliation><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Haematology and Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></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><nlm:aff id="A5">Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA</nlm:aff></affiliation></author><author><name sortKey="Chambon, Pierre" sort="Chambon, Pierre" uniqKey="Chambon P" first="Pierre" last="Chambon">Pierre Chambon</name><affiliation><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></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><nlm:aff id="A7">Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</nlm:aff></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17574023</idno><idno type="pmc">1974882</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1974882</idno><idno type="RBID">PMC:1974882</idno><idno type="doi">10.1016/j.cell.2007.05.014</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">001D47</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D47</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Microenvironment-Induced Myeloproliferative Syndrome Caused by RARγ Deficiency</title><author><name sortKey="Walkley, Carl R" sort="Walkley, Carl R" uniqKey="Walkley C" first="Carl R." last="Walkley">Carl R. Walkley</name><affiliation><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</nlm:aff></affiliation><affiliation><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></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation></author><author><name sortKey="Dworkin, Sebastian" sort="Dworkin, Sebastian" uniqKey="Dworkin S" first="Sebastian" last="Dworkin">Sebastian Dworkin</name><affiliation><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation></author><author><name sortKey="Swann, Jeremy" sort="Swann, Jeremy" uniqKey="Swann J" first="Jeremy" last="Swann">Jeremy Swann</name><affiliation><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Department of Haematology and Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></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><nlm:aff id="A5">Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA</nlm:aff></affiliation></author><author><name sortKey="Chambon, Pierre" sort="Chambon, Pierre" uniqKey="Chambon P" first="Pierre" last="Chambon">Pierre Chambon</name><affiliation><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></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><nlm:aff id="A7">Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</nlm:aff></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><nlm:aff id="A1">Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</nlm:aff></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><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0413066</journal-id><journal-id journal-id-type="pubmed-jr-id">2830</journal-id><journal-id journal-id-type="nlm-ta">Cell</journal-id><journal-title>Cell</journal-title><issn pub-type="ppub">0092-8674</issn></journal-meta><article-meta><article-id pub-id-type="pmid">17574023</article-id><article-id pub-id-type="pmc">1974882</article-id><article-id pub-id-type="doi">10.1016/j.cell.2007.05.014</article-id><article-id pub-id-type="manuscript">NIHMS25789</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A Microenvironment-Induced Myeloproliferative Syndrome Caused by RARγ Deficiency</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Walkley</surname><given-names>Carl R.</given-names></name><xref rid="A1" ref-type="aff">1</xref><xref rid="A2" ref-type="aff">2</xref><xref rid="A3" ref-type="aff">3</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Olsen</surname><given-names>Gemma Haines</given-names></name><xref rid="A1" ref-type="aff">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Dworkin</surname><given-names>Sebastian</given-names></name><xref rid="A1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Fabb</surname><given-names>Stewart A.</given-names></name><xref rid="A1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Swann</surname><given-names>Jeremy</given-names></name><xref rid="A1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>McArthur</surname><given-names>Grant A.</given-names></name><xref rid="A1" ref-type="aff">1</xref><xref rid="A2" ref-type="aff">2</xref><xref rid="A4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Westmoreland</surname><given-names>Susan V</given-names></name><xref rid="A5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Chambon</surname><given-names>Pierre</given-names></name><xref rid="A6" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Scadden</surname><given-names>David T</given-names></name><xref rid="A7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Purton</surname><given-names>Louise E.</given-names></name><xref rid="A1" ref-type="aff">1</xref><xref rid="A7" ref-type="aff">7</xref></contrib></contrib-group><aff id="A1"><label>1</label>Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</aff><aff id="A2"><label>2</label>Department of Medicine, University of Melbourne, Fitzroy, Victoria, 3065, Australia</aff><aff id="A3"><label>3</label>Department of Pediatric Oncology and Division of Hematology-Oncology, Dana-Farber Cancer Institute and Children’s Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA</aff><aff id="A4"><label>4</label>Department of Haematology and Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</aff><aff id="A5"><label>5</label>Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA</aff><aff id="A6"><label>6</label>Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, 67404 Illkirch Cedex, CU de Strasbourg, France</aff><aff id="A7"><label>7</label>Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, Boston, Massachusetts, 02114, USA</aff><author-notes><corresp id="FN1">Correspondence should be addressed to LEP: Dr. Louise Purton, Center for Regenerative Medicine, Massachusetts General Hospital, CPZN-4265A, 185 Cambridge St, Boston, MA 02114, Phone: +1 617 724 3167, Fax: +1 617 724 2662, E-mail: <email>lpurton@partners.org</email></corresp><fn id="FN2" fn-type="equal"><label>*</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>2</day><month>7</month><year>2007</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>6</month><year>2007</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>6</month><year>2008</year></pub-date><volume>129</volume><issue>6</issue><fpage>1097</fpage><lpage>1110</lpage><related-article journal-id-type="nlm-ta" journal-id="Cell" related-article-type="commentary" page="1045" id="N0x8d13d68N0x9239bdc" xlink:href="17574018" ext-link-type="pubmed" vol="129"></related-article><abstract><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></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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