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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients</title><author><name sortKey="Deininger, Michael W" sort="Deininger, Michael W" uniqKey="Deininger M" first="Michael W." last="Deininger">Michael W. Deininger</name><affiliation><nlm:aff id="aff1">Huntsman Cancer Institute University of Utah, Salt Lake City, UT;</nlm:aff></affiliation></author><author><name sortKey="Hodgson, J Graeme" sort="Hodgson, J Graeme" uniqKey="Hodgson J" first="J. Graeme" last="Hodgson">J. Graeme Hodgson</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Shah, Neil P" sort="Shah, Neil P" uniqKey="Shah N" first="Neil P." last="Shah">Neil P. Shah</name><affiliation><nlm:aff id="aff3">University of California San Francisco, San Francisco, CA;</nlm:aff></affiliation></author><author><name sortKey="Cortes, Jorge E" sort="Cortes, Jorge E" uniqKey="Cortes J" first="Jorge E." last="Cortes">Jorge E. Cortes</name><affiliation><nlm:aff id="aff4">Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff></affiliation></author><author><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name><affiliation><nlm:aff id="aff5">Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea;</nlm:aff></affiliation></author><author><name sortKey="Nicolini, Franck E" sort="Nicolini, Franck E" uniqKey="Nicolini F" first="Franck E." last="Nicolini">Franck E. Nicolini</name><affiliation><nlm:aff id="aff6">Centre Hospitalier Lyon Sud, Pierre Benite, & INSERM U1052, Lyon, France;</nlm:aff></affiliation></author><author><name sortKey="Talpaz, Moshe" sort="Talpaz, Moshe" uniqKey="Talpaz M" first="Moshe" last="Talpaz">Moshe Talpaz</name><affiliation><nlm:aff id="aff7">Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI;</nlm:aff></affiliation></author><author><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name><affiliation><nlm:aff id="aff8">Department of Hematology-Oncology “L. and A. Seragnoli,” S. Orsola-Malpighi University Hospital, Bologna, Italy;</nlm:aff></affiliation></author><author><name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Müller">Martin C. Müller</name><affiliation><nlm:aff id="aff9">III. Med. Klinik, Universitätsmedizin Mannheim, Mannheim, Germany;</nlm:aff></affiliation></author><author><name sortKey="Li, Jin" sort="Li, Jin" uniqKey="Li J" first="Jin" last="Li">Jin Li</name><affiliation><nlm:aff id="aff10">MolecularMD, Portland, OR;</nlm:aff></affiliation></author><author><name sortKey="Parker, Wendy T" sort="Parker, Wendy T" uniqKey="Parker W" first="Wendy T." last="Parker">Wendy T. Parker</name><affiliation><nlm:aff wicri:cut="; and" id="aff15">Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Lustgarten, Stephanie" sort="Lustgarten, Stephanie" uniqKey="Lustgarten S" first="Stephanie" last="Lustgarten">Stephanie Lustgarten</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Clackson, Tim" sort="Clackson, Tim" uniqKey="Clackson T" first="Tim" last="Clackson">Tim Clackson</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Haluska, Frank G" sort="Haluska, Frank G" uniqKey="Haluska F" first="Frank G." last="Haluska">Frank G. Haluska</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="Francois" last="Guilhot">Francois Guilhot</name><affiliation><nlm:aff id="aff11">INSERM Clinical Investigation Center 1402, Centre Hospitalier et Universitaire de Poitiers, France;</nlm:aff></affiliation></author><author><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name><affiliation><nlm:aff id="aff4">Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff></affiliation></author><author><name sortKey="Soverini, Simona" sort="Soverini, Simona" uniqKey="Soverini S" first="Simona" last="Soverini">Simona Soverini</name><affiliation><nlm:aff id="aff12">Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy;</nlm:aff></affiliation></author><author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name><affiliation><nlm:aff id="aff13">Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;</nlm:aff></affiliation></author><author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name><affiliation><nlm:aff id="aff14">SA Pathology and South Australian Health and Medical Research Institute, Adelaide, Australia;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff15">Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Rivera, Victor M" sort="Rivera, Victor M" uniqKey="Rivera V" first="Victor M." last="Rivera">Victor M. Rivera</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name><affiliation><nlm:aff wicri:cut="; and" id="aff15">Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff16">School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26603839</idno><idno type="pmc">4760131</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760131</idno><idno type="RBID">PMC:4760131</idno><idno type="doi">10.1182/blood-2015-08-660977</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000435</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000435</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients</title><author><name sortKey="Deininger, Michael W" sort="Deininger, Michael W" uniqKey="Deininger M" first="Michael W." last="Deininger">Michael W. Deininger</name><affiliation><nlm:aff id="aff1">Huntsman Cancer Institute University of Utah, Salt Lake City, UT;</nlm:aff></affiliation></author><author><name sortKey="Hodgson, J Graeme" sort="Hodgson, J Graeme" uniqKey="Hodgson J" first="J. Graeme" last="Hodgson">J. Graeme Hodgson</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Shah, Neil P" sort="Shah, Neil P" uniqKey="Shah N" first="Neil P." last="Shah">Neil P. Shah</name><affiliation><nlm:aff id="aff3">University of California San Francisco, San Francisco, CA;</nlm:aff></affiliation></author><author><name sortKey="Cortes, Jorge E" sort="Cortes, Jorge E" uniqKey="Cortes J" first="Jorge E." last="Cortes">Jorge E. Cortes</name><affiliation><nlm:aff id="aff4">Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff></affiliation></author><author><name sortKey="Kim, Dong Wook" sort="Kim, Dong Wook" uniqKey="Kim D" first="Dong-Wook" last="Kim">Dong-Wook Kim</name><affiliation><nlm:aff id="aff5">Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea;</nlm:aff></affiliation></author><author><name sortKey="Nicolini, Franck E" sort="Nicolini, Franck E" uniqKey="Nicolini F" first="Franck E." last="Nicolini">Franck E. Nicolini</name><affiliation><nlm:aff id="aff6">Centre Hospitalier Lyon Sud, Pierre Benite, & INSERM U1052, Lyon, France;</nlm:aff></affiliation></author><author><name sortKey="Talpaz, Moshe" sort="Talpaz, Moshe" uniqKey="Talpaz M" first="Moshe" last="Talpaz">Moshe Talpaz</name><affiliation><nlm:aff id="aff7">Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI;</nlm:aff></affiliation></author><author><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name><affiliation><nlm:aff id="aff8">Department of Hematology-Oncology “L. and A. Seragnoli,” S. Orsola-Malpighi University Hospital, Bologna, Italy;</nlm:aff></affiliation></author><author><name sortKey="Muller, Martin C" sort="Muller, Martin C" uniqKey="Muller M" first="Martin C." last="Müller">Martin C. Müller</name><affiliation><nlm:aff id="aff9">III. Med. Klinik, Universitätsmedizin Mannheim, Mannheim, Germany;</nlm:aff></affiliation></author><author><name sortKey="Li, Jin" sort="Li, Jin" uniqKey="Li J" first="Jin" last="Li">Jin Li</name><affiliation><nlm:aff id="aff10">MolecularMD, Portland, OR;</nlm:aff></affiliation></author><author><name sortKey="Parker, Wendy T" sort="Parker, Wendy T" uniqKey="Parker W" first="Wendy T." last="Parker">Wendy T. Parker</name><affiliation><nlm:aff wicri:cut="; and" id="aff15">Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Lustgarten, Stephanie" sort="Lustgarten, Stephanie" uniqKey="Lustgarten S" first="Stephanie" last="Lustgarten">Stephanie Lustgarten</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Clackson, Tim" sort="Clackson, Tim" uniqKey="Clackson T" first="Tim" last="Clackson">Tim Clackson</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Haluska, Frank G" sort="Haluska, Frank G" uniqKey="Haluska F" first="Frank G." last="Haluska">Frank G. Haluska</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Guilhot, Francois" sort="Guilhot, Francois" uniqKey="Guilhot F" first="Francois" last="Guilhot">Francois Guilhot</name><affiliation><nlm:aff id="aff11">INSERM Clinical Investigation Center 1402, Centre Hospitalier et Universitaire de Poitiers, France;</nlm:aff></affiliation></author><author><name sortKey="Kantarjian, Hagop M" sort="Kantarjian, Hagop M" uniqKey="Kantarjian H" first="Hagop M." last="Kantarjian">Hagop M. Kantarjian</name><affiliation><nlm:aff id="aff4">Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;</nlm:aff></affiliation></author><author><name sortKey="Soverini, Simona" sort="Soverini, Simona" uniqKey="Soverini S" first="Simona" last="Soverini">Simona Soverini</name><affiliation><nlm:aff id="aff12">Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy;</nlm:aff></affiliation></author><author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name><affiliation><nlm:aff id="aff13">Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;</nlm:aff></affiliation></author><author><name sortKey="Hughes, Timothy P" sort="Hughes, Timothy P" uniqKey="Hughes T" first="Timothy P." last="Hughes">Timothy P. Hughes</name><affiliation><nlm:aff id="aff14">SA Pathology and South Australian Health and Medical Research Institute, Adelaide, Australia;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff15">Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Rivera, Victor M" sort="Rivera, Victor M" uniqKey="Rivera V" first="Victor M." last="Rivera">Victor M. Rivera</name><affiliation><nlm:aff id="aff2">ARIAD Pharmaceuticals, Inc., Cambridge, MA;</nlm:aff></affiliation></author><author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name><affiliation><nlm:aff wicri:cut="; and" id="aff15">Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff16">School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia</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="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Publisher's Note:</bold> There is an <related-article id="d36e333" related-article-type="article-reference" ext-link-type="doi" xlink:href="10.1182/blood-2015-12-685149">Inside <italic>Blood</italic> Commentary</related-article> on this article in this issue.</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">26603839</article-id><article-id pub-id-type="pmc">4760131</article-id><article-id pub-id-type="publisher-id">2015/660977</article-id><article-id pub-id-type="doi">10.1182/blood-2015-08-660977</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>29</subject><subject>8</subject><subject>33</subject></subj-group><subj-group subj-group-type="heading"><subject>Clinical Trials and Observations</subject></subj-group></article-categories><title-group><article-title>Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Deininger</surname><given-names>Michael W.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hodgson</surname><given-names>J. Graeme</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Shah</surname><given-names>Neil P.</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cortes</surname><given-names>Jorge E.</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Dong-Wook</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Nicolini</surname><given-names>Franck E.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Talpaz</surname><given-names>Moshe</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Baccarani</surname><given-names>Michele</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Müller</surname><given-names>Martin C.</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Jin</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Parker</surname><given-names>Wendy T.</given-names></name><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Lustgarten</surname><given-names>Stephanie</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Clackson</surname><given-names>Tim</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Haluska</surname><given-names>Frank G.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Guilhot</surname><given-names>Francois</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Kantarjian</surname><given-names>Hagop M.</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Soverini</surname><given-names>Simona</given-names></name><xref ref-type="aff" rid="aff12">12</xref></contrib><contrib contrib-type="author"><name><surname>Hochhaus</surname><given-names>Andreas</given-names></name><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Hughes</surname><given-names>Timothy P.</given-names></name><xref ref-type="aff" rid="aff14">14</xref><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Rivera</surname><given-names>Victor M.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Branford</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="aff15">15</xref><xref ref-type="aff" rid="aff16">16</xref></contrib><aff id="aff1"><label>1</label>Huntsman Cancer Institute University of Utah, Salt Lake City, UT;</aff><aff id="aff2"><label>2</label>ARIAD Pharmaceuticals, Inc., Cambridge, MA;</aff><aff id="aff3"><label>3</label>University of California San Francisco, San Francisco, CA;</aff><aff id="aff4"><label>4</label>Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;</aff><aff id="aff5"><label>5</label>Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea;</aff><aff id="aff6"><label>6</label>Centre Hospitalier Lyon Sud, Pierre Benite, & INSERM U1052, Lyon, France;</aff><aff id="aff7"><label>7</label>Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI;</aff><aff id="aff8"><label>8</label>Department of Hematology-Oncology “L. and A. Seragnoli,” S. Orsola-Malpighi University Hospital, Bologna, Italy;</aff><aff id="aff9"><label>9</label>III. Med. Klinik, Universitätsmedizin Mannheim, Mannheim, Germany;</aff><aff id="aff10"><label>10</label>MolecularMD, Portland, OR;</aff><aff id="aff11"><label>11</label>INSERM Clinical Investigation Center 1402, Centre Hospitalier et Universitaire de Poitiers, France;</aff><aff id="aff12"><label>12</label>Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy;</aff><aff id="aff13"><label>13</label>Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;</aff><aff id="aff14"><label>14</label>SA Pathology and South Australian Health and Medical Research Institute, Adelaide, Australia;</aff><aff id="aff15"><label>15</label>Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia; and</aff><aff id="aff16"><label>16</label>School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia</aff></contrib-group><pub-date pub-type="ppub"><day>11</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="epreprint"><day>24</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>11</day><month>2</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>127</volume><issue>6</issue><fpage>703</fpage><lpage>712</lpage><history><date date-type="received"><day>07</day><month>8</month><year>2015</year></date><date date-type="accepted"><day>10</day><month>11</month><year>2015</year></date></history><permissions><copyright-statement>© 2016 by The American Society of Hematology</copyright-statement><copyright-year>2016</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="703.pdf"></self-uri><related-article id="d36e326" related-article-type="article-reference" ext-link-type="doi" xlink:href="10.1182/blood-2015-12-685149">Saglio</related-article><abstract abstract-type="teaser"><p><bold>Publisher's Note:</bold> There is an <related-article id="d36e333" related-article-type="article-reference" ext-link-type="doi" xlink:href="10.1182/blood-2015-12-685149">Inside <italic>Blood</italic> Commentary</related-article> on this article in this issue.</p></abstract><abstract abstract-type="executive-summary"><title>Key Points</title><p><list list-type="bullet"><list-item><p>Ponatinib induces durable responses regardless of baseline BCR-ABL1 mutation status in CP-CML patients.</p></list-item><list-item><p>No single or compound mutant consistently confers primary or secondary resistance to ponatinib in CP-CML.</p></list-item></list></p></abstract><abstract><p>BCR-ABL1 kinase domain mutations can confer resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In preclinical studies, clinically achievable concentrations of the third-generation BCR-ABL1 TKI ponatinib inhibit T315I and all other single BCR-ABL1 mutants except T315M, which generates a single amino acid exchange, but requires 2 sequential nucleotide exchanges. In addition, certain compound mutants (containing ≥2 mutations in cis) confer resistance. Initial analyses based largely on conventional Sanger sequencing (SS) have suggested that the preclinical relationship between BCR-ABL1 mutation status and ponatinib efficacy is generally recapitulated in patients receiving therapy. Thus far, however, such analyses have been limited by the inability of SS to definitively identify compound mutations or mutations representing less than ∼20% of total alleles (referred to as “low-level mutations”), as well as limited patient follow-up. Here we used next-generation sequencing (NGS) to define the baseline BCR-ABL1 mutation status of 267 heavily pretreated chronic phase (CP)-CML patients from the PACE trial, and used SS to identify clonally dominant mutants that may have developed on ponatinib therapy (30.1 months median follow-up). Durable cytogenetic and molecular responses were observed irrespective of baseline mutation status and included patients with compound mutations. No single or compound mutation was identified that consistently conferred primary and/or secondary resistance to ponatinib in CP-CML patients. Ponatinib is effective in CP-CML irrespective of baseline mutation status.</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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