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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting <italic>BCR-ABL</italic>
transcripts and kinase domain mutations and for expressing results</title>
<author><name sortKey="Hughes, Timothy" sort="Hughes, Timothy" uniqKey="Hughes T" first="Timothy" last="Hughes">Timothy Hughes</name>
</author>
<author><name sortKey="Deininger, Michael" sort="Deininger, Michael" uniqKey="Deininger M" first="Michael" last="Deininger">Michael Deininger</name>
</author>
<author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
</author>
<author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name>
</author>
<author><name sortKey="Radich, Jerald" sort="Radich, Jerald" uniqKey="Radich J" first="Jerald" last="Radich">Jerald Radich</name>
</author>
<author><name sortKey="Kaeda, Jaspal" sort="Kaeda, Jaspal" uniqKey="Kaeda J" first="Jaspal" last="Kaeda">Jaspal Kaeda</name>
</author>
<author><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name>
</author>
<author><name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name>
</author>
<author><name sortKey="Cross, Nicholas C P" sort="Cross, Nicholas C P" uniqKey="Cross N" first="Nicholas C. P." last="Cross">Nicholas C. P. Cross</name>
</author>
<author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name>
</author>
<author><name sortKey="Gabert, Jean" sort="Gabert, Jean" uniqKey="Gabert J" first="Jean" last="Gabert">Jean Gabert</name>
</author>
<author><name sortKey="Grimwade, David" sort="Grimwade, David" uniqKey="Grimwade D" first="David" last="Grimwade">David Grimwade</name>
</author>
<author><name sortKey="Hehlmann, Rudiger" sort="Hehlmann, Rudiger" uniqKey="Hehlmann R" first="Rüdiger" last="Hehlmann">Rüdiger Hehlmann</name>
</author>
<author><name sortKey="Kamel Reid, Suzanne" sort="Kamel Reid, Suzanne" uniqKey="Kamel Reid S" first="Suzanne" last="Kamel-Reid">Suzanne Kamel-Reid</name>
</author>
<author><name sortKey="Lipton, Jeffrey H" sort="Lipton, Jeffrey H" uniqKey="Lipton J" first="Jeffrey H." last="Lipton">Jeffrey H. Lipton</name>
</author>
<author><name sortKey="Longtine, Janina" sort="Longtine, Janina" uniqKey="Longtine J" first="Janina" last="Longtine">Janina Longtine</name>
</author>
<author><name sortKey="Martinelli, Giovanni" sort="Martinelli, Giovanni" uniqKey="Martinelli G" first="Giovanni" last="Martinelli">Giovanni Martinelli</name>
</author>
<author><name sortKey="Saglio, Giuseppe" sort="Saglio, Giuseppe" uniqKey="Saglio G" first="Giuseppe" last="Saglio">Giuseppe Saglio</name>
</author>
<author><name sortKey="Soverini, Simona" sort="Soverini, Simona" uniqKey="Soverini S" first="Simona" last="Soverini">Simona Soverini</name>
</author>
<author><name sortKey="Stock, Wendy" sort="Stock, Wendy" uniqKey="Stock W" first="Wendy" last="Stock">Wendy Stock</name>
</author>
<author><name sortKey="Goldman, John M" sort="Goldman, John M" uniqKey="Goldman J" first="John M." last="Goldman">John M. Goldman</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">16522812</idno>
<idno type="pmc">1895821</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895821</idno>
<idno type="RBID">PMC:1895821</idno>
<idno type="doi">10.1182/blood-2006-01-0092</idno>
<date when="2006">2006</date>
<idno type="wicri:Area/Pmc/Corpus">001136</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001136</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting <italic>BCR-ABL</italic>
transcripts and kinase domain mutations and for expressing results</title>
<author><name sortKey="Hughes, Timothy" sort="Hughes, Timothy" uniqKey="Hughes T" first="Timothy" last="Hughes">Timothy Hughes</name>
</author>
<author><name sortKey="Deininger, Michael" sort="Deininger, Michael" uniqKey="Deininger M" first="Michael" last="Deininger">Michael Deininger</name>
</author>
<author><name sortKey="Hochhaus, Andreas" sort="Hochhaus, Andreas" uniqKey="Hochhaus A" first="Andreas" last="Hochhaus">Andreas Hochhaus</name>
</author>
<author><name sortKey="Branford, Susan" sort="Branford, Susan" uniqKey="Branford S" first="Susan" last="Branford">Susan Branford</name>
</author>
<author><name sortKey="Radich, Jerald" sort="Radich, Jerald" uniqKey="Radich J" first="Jerald" last="Radich">Jerald Radich</name>
</author>
<author><name sortKey="Kaeda, Jaspal" sort="Kaeda, Jaspal" uniqKey="Kaeda J" first="Jaspal" last="Kaeda">Jaspal Kaeda</name>
</author>
<author><name sortKey="Baccarani, Michele" sort="Baccarani, Michele" uniqKey="Baccarani M" first="Michele" last="Baccarani">Michele Baccarani</name>
</author>
<author><name sortKey="Cortes, Jorge" sort="Cortes, Jorge" uniqKey="Cortes J" first="Jorge" last="Cortes">Jorge Cortes</name>
</author>
<author><name sortKey="Cross, Nicholas C P" sort="Cross, Nicholas C P" uniqKey="Cross N" first="Nicholas C. P." last="Cross">Nicholas C. P. Cross</name>
</author>
<author><name sortKey="Druker, Brian J" sort="Druker, Brian J" uniqKey="Druker B" first="Brian J." last="Druker">Brian J. Druker</name>
</author>
<author><name sortKey="Gabert, Jean" sort="Gabert, Jean" uniqKey="Gabert J" first="Jean" last="Gabert">Jean Gabert</name>
</author>
<author><name sortKey="Grimwade, David" sort="Grimwade, David" uniqKey="Grimwade D" first="David" last="Grimwade">David Grimwade</name>
</author>
<author><name sortKey="Hehlmann, Rudiger" sort="Hehlmann, Rudiger" uniqKey="Hehlmann R" first="Rüdiger" last="Hehlmann">Rüdiger Hehlmann</name>
</author>
<author><name sortKey="Kamel Reid, Suzanne" sort="Kamel Reid, Suzanne" uniqKey="Kamel Reid S" first="Suzanne" last="Kamel-Reid">Suzanne Kamel-Reid</name>
</author>
<author><name sortKey="Lipton, Jeffrey H" sort="Lipton, Jeffrey H" uniqKey="Lipton J" first="Jeffrey H." last="Lipton">Jeffrey H. Lipton</name>
</author>
<author><name sortKey="Longtine, Janina" sort="Longtine, Janina" uniqKey="Longtine J" first="Janina" last="Longtine">Janina Longtine</name>
</author>
<author><name sortKey="Martinelli, Giovanni" sort="Martinelli, Giovanni" uniqKey="Martinelli G" first="Giovanni" last="Martinelli">Giovanni Martinelli</name>
</author>
<author><name sortKey="Saglio, Giuseppe" sort="Saglio, Giuseppe" uniqKey="Saglio G" first="Giuseppe" last="Saglio">Giuseppe Saglio</name>
</author>
<author><name sortKey="Soverini, Simona" sort="Soverini, Simona" uniqKey="Soverini S" first="Simona" last="Soverini">Simona Soverini</name>
</author>
<author><name sortKey="Stock, Wendy" sort="Stock, Wendy" uniqKey="Stock W" first="Wendy" last="Stock">Wendy Stock</name>
</author>
<author><name sortKey="Goldman, John M" sort="Goldman, John M" uniqKey="Goldman J" first="John M." last="Goldman">John M. Goldman</name>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2006">2006</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The introduction in 1998 of imatinib mesylate (IM) revolutionized management of patients with chronic myeloid leukemia (CML) and the second generation of tyrosine kinase inhibitors may prove superior to IM. Real-time quantitative polymerase chain reaction (RQ-PCR) provides an accurate measure of the total leukemiacell mass and the degree to which <italic>BCR-ABL</italic>
transcripts are reduced by therapy correlates with progression-free survival. Because a rising level of <italic>BCR-ABL</italic>
is an early indication of loss of response and thus the need to reassess therapeutic strategy, regular molecular monitoring of individual patients is clearly desirable. Here we summarize the results of a consensus meeting that took place at the National Institutes of Health (NIH) in Bethesda in October 2005. We make suggestions for (1) harmonizing the differing methodologies for measuring <italic>BCR-ABL</italic>
transcripts in patients with CML undergoing treatment and using a conversion factor whereby individual laboratories can express <italic>BCR-ABL</italic>
transcript levels on an internationally agreed scale; (2) using serial RQ-PCR results rather than bone marrow cytogenetics or fluorescence in situ hybridization (FISH) for the <italic>BCR-ABL</italic>
gene to monitor individual patients responding to treatment; and (3) detecting and reporting Philadelphia (Ph) chromosome-positive subpopulations bearing <italic>BCR-ABL</italic>
kinase domain mutations. We recognize that our recommendations are provisional and will require revision as new evidence emerges. (Blood. 2006;108:28-37)</p>
</div>
</front>
</TEI>
<pmc article-type="review-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="publisher-id">bloodjournal</journal-id>
<journal-title>Blood</journal-title>
<issn pub-type="ppub">0006-4971</issn>
<issn pub-type="epub">1528-0020</issn>
<publisher><publisher-name>The American Society of Hematology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">16522812</article-id>
<article-id pub-id-type="pmc">1895821</article-id>
<article-id pub-id-type="publisher-id">0028</article-id>
<article-id pub-id-type="doi">10.1182/blood-2006-01-0092</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review in Translational Hematology</subject>
</subj-group>
</article-categories>
<title-group><article-title>Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting <italic>BCR-ABL</italic>
transcripts and kinase domain mutations and for expressing results</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hughes</surname>
<given-names>Timothy</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Deininger</surname>
<given-names>Michael</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Hochhaus</surname>
<given-names>Andreas</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Branford</surname>
<given-names>Susan</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Radich</surname>
<given-names>Jerald</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kaeda</surname>
<given-names>Jaspal</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Baccarani</surname>
<given-names>Michele</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Cortes</surname>
<given-names>Jorge</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Cross</surname>
<given-names>Nicholas C. P.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Druker</surname>
<given-names>Brian J.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Gabert</surname>
<given-names>Jean</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Grimwade</surname>
<given-names>David</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Hehlmann</surname>
<given-names>Rüdiger</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kamel-Reid</surname>
<given-names>Suzanne</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Lipton</surname>
<given-names>Jeffrey H.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Longtine</surname>
<given-names>Janina</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Martinelli</surname>
<given-names>Giovanni</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Saglio</surname>
<given-names>Giuseppe</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Soverini</surname>
<given-names>Simona</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Stock</surname>
<given-names>Wendy</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Goldman</surname>
<given-names>John M.</given-names>
</name>
</contrib>
</contrib-group>
<aff id="N0x8c6c6f0N0x8e6f6bc">From the Institute of Medical and Veterinary Science, Adelaide, Australia; Department of Hematology/Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, OR; Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Haematology, Imperial College at Hammersmith Hospital, London, United Kingdom; Institute of Hematology and Medical Oncology “Seragnoli,” University of Bologna, Italy; Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, TX; National Genetics Reference Laboratory, University of Southampton, Salisbury, United Kingdom; Assistance Publique des Hopitaux de Marseille (APHM) and Equipe de Recherche Technologique (ERT), University de la Mediterranée, Marseille, France; Department of Medical and Molecular Genetics, King's College, London, United Kingdom; Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada; Department of Pathology, Brigham and Women's Hospital, Boston, MA; Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy; Department of Medicine, University of Chicago, Chicago, IL; and the Hematology Branch, National Heart, Lung & Blood Institute, National Institutes of Health (NIH), Bethesda, MD.</aff>
<author-notes><fn><p><bold>Reprints:</bold>
John Goldman, Hematology Branch, NHLBI, Bldg 10, Rm 3-5140, 10 Center Dr, Bethesda MD 20892-1202; e-mail: <email>goldmanj2@nhlbi.nih.gov</email>
. </p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>1</day>
<month>7</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="epreprint"><day>7</day>
<month>3</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>7</month>
<year>2007</year>
</pub-date>
<volume>108</volume>
<issue>1</issue>
<fpage>28</fpage>
<lpage>37</lpage>
<history><date date-type="received"><day>10</day>
<month>1</month>
<year>2006</year>
</date>
<date date-type="accepted"><day>18</day>
<month>2</month>
<year>2006</year>
</date>
</history>
<copyright-statement>Copyright © 2006, The American Society of Hematology</copyright-statement>
<copyright-year>2006</copyright-year>
<self-uri xlink:title="pdf" xlink:href="zh801306000028.pdf"></self-uri>
<abstract><p>The introduction in 1998 of imatinib mesylate (IM) revolutionized management of patients with chronic myeloid leukemia (CML) and the second generation of tyrosine kinase inhibitors may prove superior to IM. Real-time quantitative polymerase chain reaction (RQ-PCR) provides an accurate measure of the total leukemiacell mass and the degree to which <italic>BCR-ABL</italic>
transcripts are reduced by therapy correlates with progression-free survival. Because a rising level of <italic>BCR-ABL</italic>
is an early indication of loss of response and thus the need to reassess therapeutic strategy, regular molecular monitoring of individual patients is clearly desirable. Here we summarize the results of a consensus meeting that took place at the National Institutes of Health (NIH) in Bethesda in October 2005. We make suggestions for (1) harmonizing the differing methodologies for measuring <italic>BCR-ABL</italic>
transcripts in patients with CML undergoing treatment and using a conversion factor whereby individual laboratories can express <italic>BCR-ABL</italic>
transcript levels on an internationally agreed scale; (2) using serial RQ-PCR results rather than bone marrow cytogenetics or fluorescence in situ hybridization (FISH) for the <italic>BCR-ABL</italic>
gene to monitor individual patients responding to treatment; and (3) detecting and reporting Philadelphia (Ph) chromosome-positive subpopulations bearing <italic>BCR-ABL</italic>
kinase domain mutations. We recognize that our recommendations are provisional and will require revision as new evidence emerges. (Blood. 2006;108:28-37)</p>
</abstract>
</article-meta>
<notes><fn-group><fn><p><italic>Blood</italic>
First Edition Paper, prepublished online March 7, 2006; DOI 10.1182/blood-2006-01-0092.</p>
</fn>
<fn><p>Supported by unrestricted educational grants from Novartis Pharma (Basel, Switzerland) and Bristol-Myers Squibb (Wallingford, CT) to the Foundation for the National Institutes of Health. A.H., J.K., M.B., N.C.P.C., J.G., D.G., R.H., G.M., G.S., and S.S. were supported by the European Leukemia Net within the Sixth European Community Framework Programme for Research and Technological Development.</p>
</fn>
<fn><p>T.H and S.B. provided the initial draft of the section of methodology for RQ-PCR; M.D. provided the initial draft for the section on KD mutations; and R.H. and M.B. contributed drafts for the clinical monitoring section. All other named authors attended at least 1 meeting and in most cases 2 separate meetings to discuss the content of the manuscript, and all authors read and made constructive comments and corrections on at least 2 and more often 3 to 4 versions of the manuscript during its prepration. J.M.G. prepared a series of drafts leading ultimately to the final manuscript.</p>
</fn>
</fn-group>
</notes>
</front>
</pmc>
</record>
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