{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:58:27Z","timestamp":1777456707018,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T00:00:00Z","timestamp":1381363200000},"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":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Approximately one\u2010third of patients with chronic myeloid leukaemia will fail to achieve or maintain responses to imatinib. Changes in solute carrier family 22 (organic cation transporter), member 1 (<jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>22<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1, also termed <jats:styled-content style=\"fixed-case\">OCT<\/jats:styled-content>1), the main transporter for imatinib, have been proposed as a possible predictive factor. We analysed <jats:italic>SLC22A1<\/jats:italic> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels and single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) located in exon 7 in 153 diagnostic whole blood samples from two patient cohorts. The level of <jats:italic>SLC22A1<\/jats:italic> expression did not significantly correlate with imatinib failure or achievement of molecular remission. The <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> 408V&gt;M (g.1222G&gt;A) was present in 65% of patients and was associated in all cases with an eight base\u2010pair insertion (8<jats:sup>+<\/jats:sup> allele) at the 3\u2032 end of exon 7. The latter generates an alternative splice site, leading to a premature stop codon. <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>420del was found in 33% of patients and never in <jats:italic>cis<\/jats:italic> with 8<jats:sup>+<\/jats:sup> (the 3<jats:sup>\u2212<\/jats:sup> allele). Significantly longer times to 1% and 0\u00b71% molecular responses (by quantitative reverse transcription polymerase chain reaction) were seen in patients with 8<jats:sup>+<\/jats:sup>8<jats:sup>+<\/jats:sup> or 8<jats:sup>+<\/jats:sup>N compared to those with the remaining four genotypes (N\u00a0=\u00a0no insertion or deletion). Patients lacking 8<jats:sup>+<\/jats:sup> and 3<jats:sup>\u2212<\/jats:sup> (NN, 18%) showed the best outcomes overall. Thus, while <jats:italic><jats:styled-content style=\"fixed-case\">SLC<\/jats:styled-content>22<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1<\/jats:italic> expression does not appear to affect response, alterations in its splicing or amino acid sequence may do so.<\/jats:p>","DOI":"10.1111\/bjh.12591","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:56:19Z","timestamp":1381542979000},"page":"631-639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A common novel splice variant of <i><scp>SLC<\/scp>22<scp>A<\/scp>1<\/i> (<i><scp>OCT<\/scp>1)<\/i> is associated with impaired responses to imatinib in patients with chronic myeloid leukaemia"],"prefix":"10.1111","volume":"163","author":[{"given":"Jacob","family":"Grinfeld","sequence":"first","affiliation":[{"name":"Department of Haematology Imperial College Healthcare NHS Trust London 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