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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hemostatic disorders in a JAK2<sup>V617F</sup>-driven mouse model of myeloproliferative neoplasm</title><author><name sortKey="Lamrani, Lamia" sort="Lamrani, Lamia" uniqKey="Lamrani L" first="Lamia" last="Lamrani">Lamia Lamrani</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Lacout, Catherine" sort="Lacout, Catherine" uniqKey="Lacout C" first="Catherine" last="Lacout">Catherine Lacout</name><affiliation><nlm:aff id="aff3">INSERM, U1009, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Institut Gustave Roussy, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Ollivier, Veronique" sort="Ollivier, Veronique" uniqKey="Ollivier V" first="Véronique" last="Ollivier">Véronique Ollivier</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Denis, Cecile V" sort="Denis, Cecile V" uniqKey="Denis C" first="Cécile V." last="Denis">Cécile V. Denis</name><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff6">INSERM, U770, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Gardiner, Elizabeth" sort="Gardiner, Elizabeth" uniqKey="Gardiner E" first="Elizabeth" last="Gardiner">Elizabeth Gardiner</name><affiliation><nlm:aff id="aff7">Monash University, Clayton, VIC, Australia</nlm:aff></affiliation></author><author><name sortKey="Ho Tin Noe, Benoit" sort="Ho Tin Noe, Benoit" uniqKey="Ho Tin Noe B" first="Benoit" last="Ho Tin Noe">Benoit Ho Tin Noe</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Vainchenker, William" sort="Vainchenker, William" uniqKey="Vainchenker W" first="William" last="Vainchenker">William Vainchenker</name><affiliation><nlm:aff id="aff3">INSERM, U1009, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Institut Gustave Roussy, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Villeval, Jean Luc" sort="Villeval, Jean Luc" uniqKey="Villeval J" first="Jean-Luc" last="Villeval">Jean-Luc Villeval</name><affiliation><nlm:aff id="aff3">INSERM, U1009, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Institut Gustave Roussy, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Jandrot Perrus, Martine" sort="Jandrot Perrus, Martine" uniqKey="Jandrot Perrus M" first="Martine" last="Jandrot-Perrus">Martine Jandrot-Perrus</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24951423</idno><idno type="pmc">4133486</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133486</idno><idno type="RBID">PMC:4133486</idno><idno type="doi">10.1182/blood-2013-10-530832</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001803</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001803</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Hemostatic disorders in a JAK2<sup>V617F</sup>-driven mouse model of myeloproliferative neoplasm</title><author><name sortKey="Lamrani, Lamia" sort="Lamrani, Lamia" uniqKey="Lamrani L" first="Lamia" last="Lamrani">Lamia Lamrani</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Lacout, Catherine" sort="Lacout, Catherine" uniqKey="Lacout C" first="Catherine" last="Lacout">Catherine Lacout</name><affiliation><nlm:aff id="aff3">INSERM, U1009, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Institut Gustave Roussy, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Ollivier, Veronique" sort="Ollivier, Veronique" uniqKey="Ollivier V" first="Véronique" last="Ollivier">Véronique Ollivier</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Denis, Cecile V" sort="Denis, Cecile V" uniqKey="Denis C" first="Cécile V." last="Denis">Cécile V. Denis</name><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff6">INSERM, U770, Le Kremlin-Bicêtre, France</nlm:aff></affiliation></author><author><name sortKey="Gardiner, Elizabeth" sort="Gardiner, Elizabeth" uniqKey="Gardiner E" first="Elizabeth" last="Gardiner">Elizabeth Gardiner</name><affiliation><nlm:aff id="aff7">Monash University, Clayton, VIC, Australia</nlm:aff></affiliation></author><author><name sortKey="Ho Tin Noe, Benoit" sort="Ho Tin Noe, Benoit" uniqKey="Ho Tin Noe B" first="Benoit" last="Ho Tin Noe">Benoit Ho Tin Noe</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Vainchenker, William" sort="Vainchenker, William" uniqKey="Vainchenker W" first="William" last="Vainchenker">William Vainchenker</name><affiliation><nlm:aff id="aff3">INSERM, U1009, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Institut Gustave Roussy, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Villeval, Jean Luc" sort="Villeval, Jean Luc" uniqKey="Villeval J" first="Jean-Luc" last="Villeval">Jean-Luc Villeval</name><affiliation><nlm:aff id="aff3">INSERM, U1009, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Université Paris-Sud 11, Villejuif, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Institut Gustave Roussy, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Jandrot Perrus, Martine" sort="Jandrot Perrus, Martine" uniqKey="Jandrot Perrus M" first="Martine" last="Jandrot-Perrus">Martine Jandrot-Perrus</name><affiliation><nlm:aff id="aff1">INSERM, U1148, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Université Paris Denis Diderot 7, Paris, France;</nlm:aff></affiliation></author></analytic><series><title level="j">Blood</title><idno type="ISSN">0006-4971</idno><idno type="eISSN">1528-0020</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Key Points</title><p><list list-type="bullet"><list-item><p>Mice constitutively developing a JAK2<sup>V617F</sup>-induced PV exhibit a bleeding tendency combined with the accelerated formation of unstable clots.</p></list-item><list-item><p>Hemostatic defects are not concomitant with JAK2<sup>V617F</sup> expression, suggesting they are not directly caused by the mutation.</p></list-item></list></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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Blood</journal-id><journal-id journal-id-type="iso-abbrev">Blood</journal-id><journal-id journal-id-type="hwp">bloodjournal</journal-id><journal-id journal-id-type="pmc">blood</journal-id><journal-id journal-id-type="publisher-id">Blood</journal-id><journal-title-group><journal-title>Blood</journal-title></journal-title-group><issn pub-type="ppub">0006-4971</issn><issn pub-type="epub">1528-0020</issn><publisher><publisher-name>American Society of Hematology</publisher-name><publisher-loc>Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24951423</article-id><article-id pub-id-type="pmc">4133486</article-id><article-id pub-id-type="publisher-id">2013/530832</article-id><article-id pub-id-type="doi">10.1182/blood-2013-10-530832</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>33</subject><subject>35</subject></subj-group><subj-group subj-group-type="heading"><subject>Platelets and Thrombopoiesis</subject></subj-group></article-categories><title-group><article-title>Hemostatic disorders in a JAK2<sup>V617F</sup>-driven mouse model of myeloproliferative neoplasm</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lamrani</surname><given-names>Lamia</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lacout</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Ollivier</surname><given-names>Véronique</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Denis</surname><given-names>Cécile V.</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Gardiner</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Ho Tin Noe</surname><given-names>Benoit</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Vainchenker</surname><given-names>William</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Villeval</surname><given-names>Jean-Luc</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Jandrot-Perrus</surname><given-names>Martine</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><aff id="aff1"><label>1</label>INSERM, U1148, Paris, France;</aff><aff id="aff2"><label>2</label>Université Paris Denis Diderot 7, Paris, France;</aff><aff id="aff3"><label>3</label>INSERM, U1009, Villejuif, France;</aff><aff id="aff4"><label>4</label>Université Paris-Sud 11, Villejuif, France;</aff><aff id="aff5"><label>5</label>Institut Gustave Roussy, Villejuif, France;</aff><aff id="aff6"><label>6</label>INSERM, U770, Le Kremlin-Bicêtre, France; and</aff><aff id="aff7"><label>7</label>Monash University, Clayton, VIC, Australia</aff></contrib-group><pub-date pub-type="ppub"><day>14</day><month>8</month><year>2014</year></pub-date><pub-date pub-type="epreprint"><day>20</day><month>6</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>14</day><month>8</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>124</volume><issue>7</issue><fpage>1136</fpage><lpage>1145</lpage><history><date date-type="received"><day>07</day><month>10</month><year>2013</year></date><date date-type="accepted"><day>02</day><month>6</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 by The American Society of Hematology</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="1136.pdf"></self-uri><related-article related-article-type="article-reference" id="d35e211" vol="124" page="992" issue="7" ext-link-type="pmc"></related-article><abstract abstract-type="executive-summary"><title>Key Points</title><p><list list-type="bullet"><list-item><p>Mice constitutively developing a JAK2<sup>V617F</sup>-induced PV exhibit a bleeding tendency combined with the accelerated formation of unstable clots.</p></list-item><list-item><p>Hemostatic defects are not concomitant with JAK2<sup>V617F</sup> expression, suggesting they are not directly caused by the mutation.</p></list-item></list></p></abstract><abstract><p>Thrombosis is common in patients suffering from myeloproliferative neoplasm (MPN), whereas bleeding is less frequent. JAK2<sup>V617F</sup>, the main mutation involved in MPN, is considered as a risk factor for thrombosis, although the direct link between the mutation and hemostatic disorders is not strictly established. We investigated this question using conditional JAK2<sup>V617F</sup> knock-in mice with constitutive and inducible expression of JAK2<sup>V617F</sup> in hematopoietic cells, which develop a polycythemia vera (PV)-like disorder evolving into myelofibrosis. In vitro, thrombosis was markedly impaired with an 80% decrease in platelet-covered surface, when JAK2<sup>V617F</sup> blood was perfused at arterial shear over collagen. JAK2<sup>V617F</sup> platelets presented only a moderate glycoprotein (GP) VI deficiency not responsible for the defective platelet accumulation. In contrast, a decreased proportion of high-molecular-weight von Willebrand factor multimers could reduce platelet adhesion. Accordingly, the tail bleeding time was prolonged. In the FeCl<sub>3</sub>-induced thrombosis model, platelet aggregates formed rapidly but were highly unstable. Interestingly, vessels were considerably dilated. Thus, mice developing PV secondary to constitutive JAK2<sup>V617F</sup> expression exhibit a bleeding tendency combined with the accelerated formation of unstable clots, reminiscent of observations made in patients. Hemostatic defects were not concomitant with the induction of JAK2<sup>V617F</sup> expression, suggesting they were not directly caused by the mutation but were rather the consequence of perturbations in blood and vessel homeostasis.</p></abstract><counts><page-count count="10"></page-count></counts><custom-meta-group><custom-meta><meta-name>access</meta-name><meta-value>free</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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