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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression</title><author><name sortKey="Beer, Philip A" sort="Beer, Philip A" uniqKey="Beer P" first="Philip A." last="Beer">Philip A. Beer</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Knapp, David J H F" sort="Knapp, David J H F" uniqKey="Knapp D" first="David J. H. F." last="Knapp">David J. H. F. Knapp</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Miller, Paul H" sort="Miller, Paul H" uniqKey="Miller P" first="Paul H." last="Miller">Paul H. Miller</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Kannan, Nagarajan" sort="Kannan, Nagarajan" uniqKey="Kannan N" first="Nagarajan" last="Kannan">Nagarajan Kannan</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Sloma, Ivan" sort="Sloma, Ivan" uniqKey="Sloma I" first="Ivan" last="Sloma">Ivan Sloma</name><affiliation><nlm:aff id="aff2">Laboratoire d’Hématologie, Hôpital Paul Brousse, Assistance Publique des Hôpitaux de Paris, INSERM U935, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Heel, Kathy" sort="Heel, Kathy" uniqKey="Heel K" first="Kathy" last="Heel">Kathy Heel</name><affiliation><nlm:aff id="aff3">School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley WA, Australia;</nlm:aff></affiliation></author><author><name sortKey="Babovic, Sonja" sort="Babovic, Sonja" uniqKey="Babovic S" first="Sonja" last="Babovic">Sonja Babovic</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Bulaeva, Elizabeth" sort="Bulaeva, Elizabeth" uniqKey="Bulaeva E" first="Elizabeth" last="Bulaeva">Elizabeth Bulaeva</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Rabu, Gabrielle" sort="Rabu, Gabrielle" uniqKey="Rabu G" first="Gabrielle" last="Rabu">Gabrielle Rabu</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Terry, Jefferson" sort="Terry, Jefferson" uniqKey="Terry J" first="Jefferson" last="Terry">Jefferson Terry</name><affiliation><nlm:aff id="aff4">Department of Pathology and Molecular Medicine, McMaster University Medical Centre, Hamilton, ON, Canada;</nlm:aff></affiliation></author><author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Knight Cancer Institute, Oregon Health & Science University, Portland, OR</nlm:aff></affiliation></author><author><name sortKey="Loriaux, Marc M" sort="Loriaux, Marc M" uniqKey="Loriaux M" first="Marc M." last="Loriaux">Marc M. Loriaux</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Knight Cancer Institute, Oregon Health & Science University, Portland, OR</nlm:aff></affiliation></author><author><name sortKey="Loeb, Keith R" sort="Loeb, Keith R" uniqKey="Loeb K" first="Keith R." last="Loeb">Keith R. Loeb</name><affiliation><nlm:aff id="aff6">Fred Hutchinson Cancer Research Center, Seattle, WA</nlm:aff></affiliation></author><author><name sortKey="Radich, Jerald P" sort="Radich, Jerald P" uniqKey="Radich J" first="Jerald P." last="Radich">Jerald P. Radich</name><affiliation><nlm:aff id="aff6">Fred Hutchinson Cancer Research Center, Seattle, WA</nlm:aff></affiliation></author><author><name sortKey="Erber, Wendy N" sort="Erber, Wendy N" uniqKey="Erber W" first="Wendy N." last="Erber">Wendy N. Erber</name><affiliation><nlm:aff id="aff3">School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley WA, Australia;</nlm:aff></affiliation></author><author><name sortKey="Eaves, Connie J" sort="Eaves, Connie J" uniqKey="Eaves C" first="Connie J." last="Eaves">Connie J. Eaves</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25370416</idno><idno type="pmc">4300391</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300391</idno><idno type="RBID">PMC:4300391</idno><idno type="doi">10.1182/blood-2014-06-581173</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001806</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001806</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression</title><author><name sortKey="Beer, Philip A" sort="Beer, Philip A" uniqKey="Beer P" first="Philip A." last="Beer">Philip A. Beer</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Knapp, David J H F" sort="Knapp, David J H F" uniqKey="Knapp D" first="David J. H. F." last="Knapp">David J. H. F. Knapp</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Miller, Paul H" sort="Miller, Paul H" uniqKey="Miller P" first="Paul H." last="Miller">Paul H. Miller</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Kannan, Nagarajan" sort="Kannan, Nagarajan" uniqKey="Kannan N" first="Nagarajan" last="Kannan">Nagarajan Kannan</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Sloma, Ivan" sort="Sloma, Ivan" uniqKey="Sloma I" first="Ivan" last="Sloma">Ivan Sloma</name><affiliation><nlm:aff id="aff2">Laboratoire d’Hématologie, Hôpital Paul Brousse, Assistance Publique des Hôpitaux de Paris, INSERM U935, Villejuif, France;</nlm:aff></affiliation></author><author><name sortKey="Heel, Kathy" sort="Heel, Kathy" uniqKey="Heel K" first="Kathy" last="Heel">Kathy Heel</name><affiliation><nlm:aff id="aff3">School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley WA, Australia;</nlm:aff></affiliation></author><author><name sortKey="Babovic, Sonja" sort="Babovic, Sonja" uniqKey="Babovic S" first="Sonja" last="Babovic">Sonja Babovic</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Bulaeva, Elizabeth" sort="Bulaeva, Elizabeth" uniqKey="Bulaeva E" first="Elizabeth" last="Bulaeva">Elizabeth Bulaeva</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Rabu, Gabrielle" sort="Rabu, Gabrielle" uniqKey="Rabu G" first="Gabrielle" last="Rabu">Gabrielle Rabu</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</nlm:aff></affiliation></author><author><name sortKey="Terry, Jefferson" sort="Terry, Jefferson" uniqKey="Terry J" first="Jefferson" last="Terry">Jefferson Terry</name><affiliation><nlm:aff id="aff4">Department of Pathology and Molecular Medicine, McMaster University Medical Centre, Hamilton, ON, Canada;</nlm:aff></affiliation></author><author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Knight Cancer Institute, Oregon Health & Science University, Portland, OR</nlm:aff></affiliation></author><author><name sortKey="Loriaux, Marc M" sort="Loriaux, Marc M" uniqKey="Loriaux M" first="Marc M." last="Loriaux">Marc M. Loriaux</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Knight Cancer Institute, Oregon Health & Science University, Portland, OR</nlm:aff></affiliation></author><author><name sortKey="Loeb, Keith R" sort="Loeb, Keith R" uniqKey="Loeb K" first="Keith R." last="Loeb">Keith R. Loeb</name><affiliation><nlm:aff id="aff6">Fred Hutchinson Cancer Research Center, Seattle, WA</nlm:aff></affiliation></author><author><name sortKey="Radich, Jerald P" sort="Radich, Jerald P" uniqKey="Radich J" first="Jerald P." last="Radich">Jerald P. Radich</name><affiliation><nlm:aff id="aff6">Fred Hutchinson Cancer Research Center, Seattle, WA</nlm:aff></affiliation></author><author><name sortKey="Erber, Wendy N" sort="Erber, Wendy N" uniqKey="Erber W" first="Wendy N." last="Erber">Wendy N. Erber</name><affiliation><nlm:aff id="aff3">School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley WA, Australia;</nlm:aff></affiliation></author><author><name sortKey="Eaves, Connie J" sort="Eaves, Connie J" uniqKey="Eaves C" first="Connie J." last="Eaves">Connie J. Eaves</name><affiliation><nlm:aff id="aff1">Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</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="2015">2015</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>CML patients with advanced-phase myeloid disease frequently show decreased IKAROS protein in primitive cells.</p></list-item><list-item><p>Expression of a dominant-negative IKAROS isoform expands primitive human CML cells and enhances their differentiation into basophils.</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">25370416</article-id><article-id pub-id-type="pmc">4300391</article-id><article-id pub-id-type="publisher-id">2014/581173</article-id><article-id pub-id-type="doi">10.1182/blood-2014-06-581173</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>33</subject></subj-group><subj-group subj-group-type="heading"><subject>Myeloid Neoplasia</subject></subj-group></article-categories><title-group><article-title>Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Beer</surname><given-names>Philip A.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Knapp</surname><given-names>David J. H. F.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>Paul H.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kannan</surname><given-names>Nagarajan</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sloma</surname><given-names>Ivan</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Heel</surname><given-names>Kathy</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Babovic</surname><given-names>Sonja</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bulaeva</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rabu</surname><given-names>Gabrielle</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Terry</surname><given-names>Jefferson</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Druker</surname><given-names>Brian J.</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Loriaux</surname><given-names>Marc M.</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Loeb</surname><given-names>Keith R.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Radich</surname><given-names>Jerald P.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Erber</surname><given-names>Wendy N.</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Eaves</surname><given-names>Connie J.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><aff id="aff1"><label>1</label>Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada;</aff><aff id="aff2"><label>2</label>Laboratoire d’Hématologie, Hôpital Paul Brousse, Assistance Publique des Hôpitaux de Paris, INSERM U935, Villejuif, France;</aff><aff id="aff3"><label>3</label>School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley WA, Australia;</aff><aff id="aff4"><label>4</label>Department of Pathology and Molecular Medicine, McMaster University Medical Centre, Hamilton, ON, Canada;</aff><aff id="aff5"><label>5</label>Knight Cancer Institute, Oregon Health & Science University, Portland, OR; and</aff><aff id="aff6"><label>6</label>Fred Hutchinson Cancer Research Center, Seattle, WA</aff></contrib-group><pub-date pub-type="ppub"><day>15</day><month>1</month><year>2015</year></pub-date><pub-date pub-type="epreprint"><day>04</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>1</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>125</volume><issue>3</issue><fpage>504</fpage><lpage>515</lpage><history><date date-type="received"><day>09</day><month>6</month><year>2014</year></date><date date-type="accepted"><day>29</day><month>10</month><year>2014</year></date></history><permissions><copyright-statement>© 2015 by The American Society of Hematology</copyright-statement><copyright-year>2015</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="504.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Key Points</title><p><list list-type="bullet"><list-item><p>CML patients with advanced-phase myeloid disease frequently show decreased IKAROS protein in primitive cells.</p></list-item><list-item><p>Expression of a dominant-negative IKAROS isoform expands primitive human CML cells and enhances their differentiation into basophils.</p></list-item></list></p></abstract><abstract><p>Without effective therapy, chronic-phase chronic myeloid leukemia (CP-CML) evolves into an acute leukemia (blast crisis [BC]) that displays either myeloid or B-lymphoid characteristics. This transition is often preceded by a clinically recognized, but biologically poorly characterized, accelerated phase (AP). Here, we report that IKAROS protein is absent or reduced in bone marrow blasts from most CML patients with advanced myeloid disease (AP or BC). This contrasts with primitive CP-CML cells and BCR-ABL1–negative acute myeloid leukemia blasts, which express readily detectable IKAROS. To investigate whether loss of IKAROS contributes to myeloid disease progression in CP-CML, we examined the effects of forced expression of a dominant-negative isoform of IKAROS (IK6) in CP-CML patients’ CD34<sup>+</sup> cells. We confirmed that IK6 disrupts IKAROS activity in transduced CP-CML cells and showed that it confers on them features of AP-CML, including a prolonged increased output in vitro and in xenografted mice of primitive cells with an enhanced ability to differentiate into basophils. Expression of IK6 in CD34<sup>+</sup> CP-CML cells also led to activation of signal transducer and activator of transcription 5 and transcriptional repression of its negative regulators. These findings implicate loss of IKAROS as a frequent step and potential diagnostic harbinger of progressive myeloid disease in CML patients.</p></abstract><counts><page-count count="12"></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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