{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T05:40:33Z","timestamp":1696311633292},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T00:00:00Z","timestamp":1386201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The exact disease state of chronic myeloid leukaemia (<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>34<jats:sup>+<\/jats:sup> stem cell and progenitor cell subpopulations were isolated by fluorescence\u2010activated cell sorting (<jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content>), and their content of residual Philadelphia positive (<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>h<jats:sup>+<\/jats:sup>) cells was evaluated in 17 <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> patients (major molecular response, <jats:italic>n<\/jats:italic>\u00a0=\u00a06; 4\u2010log reduction in <jats:italic><jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1<\/jats:italic> expression (<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content><jats:sup>4<\/jats:sup>), <jats:italic>n<\/jats:italic>\u00a0=\u00a011) using both sensitive <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> and interphase fluorescence <jats:italic>in situ<\/jats:italic> hybridization (<jats:styled-content style=\"fixed-case\">iFISH<\/jats:styled-content>). Despite evaluating fewer cells, <jats:styled-content style=\"fixed-case\">iFISH<\/jats:styled-content> proved superior to <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\u2010based <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> in detecting residual <jats:styled-content style=\"fixed-case\">Ph<\/jats:styled-content><jats:sup>+<\/jats:sup> stem cells (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7005), and detected Ph<jats:sup>+<\/jats:sup> stem\u2010 and progenitor cells in 9\/10 patients at frequencies of 2\u201314%. Moreover, while all <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content><jats:sup>+<\/jats:sup> samples also were <jats:styled-content style=\"fixed-case\">iFISH<\/jats:styled-content><jats:sup>+<\/jats:sup>, 9\/33 samples were <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>\u2010\/<jats:styled-content style=\"fixed-case\">iFISH<\/jats:styled-content><jats:sup>+<\/jats:sup>, including all positive samples from <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content><jats:sup>4<\/jats:sup> patients. Our findings show that residual <jats:styled-content style=\"fixed-case\">Ph<\/jats:styled-content><jats:sup>+<\/jats:sup> cells are low <jats:italic><jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1<\/jats:italic> producers, and that <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010based methods are required to assess the content of persisting <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>h<jats:sup>+<\/jats:sup> stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in <jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content> patients in <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content><jats:sup>4<\/jats:sup>, and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.<\/jats:p>","DOI":"10.1111\/bjh.12589","type":"journal-article","created":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T07:27:27Z","timestamp":1386228447000},"page":"53-60","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cell sorting enables interphase fluorescence <i>in situ<\/i> hybridization detection of low <scp><i>BCR\u2010ABL<\/i><\/scp><i>1<\/i> producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission"],"prefix":"10.1111","volume":"164","author":[{"given":"Peter B.","family":"van Kooten Niekerk","sequence":"first","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"The FACS Core Facility Aarhus University Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte G.","family":"Nyvold","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans B.","family":"Ommen","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne S.","family":"Roug","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Line","family":"Nederby","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hokland","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eigil","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital Aarhus 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