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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
. </pmc-comment>
<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>
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