{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:55:26Z","timestamp":1791287726683,"version":"4.3.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T00:00:00Z","timestamp":1359936000000},"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":[[2013,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>This study explored the anti\u2010leukaemic efficacy of novel irreversible inhibitors of the major nuclear export receptor, chromosome region maintenance 1 (<jats:styled-content style=\"fixed-case\">CRM<\/jats:styled-content>1, also termed <jats:styled-content style=\"fixed-case\">XPO<\/jats:styled-content>1). We found that these novel <jats:styled-content style=\"fixed-case\">CRM<\/jats:styled-content>1 antagonists, termed <jats:styled-content style=\"fixed-case\">SINE<\/jats:styled-content> (Selective Inhibitors of Nuclear Export), induced rapid apoptosis at low nanomolar concentrations in a panel of 14 human <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell acute lymphoblastic leukaemia (<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>) cell lines representing different molecular subtypes of the disease. To assess <jats:italic>in vivo<\/jats:italic> anti\u2010leukaemia cell activity, we engrafted immunodeficient mice intravenously with the human <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL MOLT<\/jats:styled-content>\u20104 cells, which harbour activating mutations of <jats:italic><jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic> as well as loss of function of the <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic> tumour suppressors and express a high level of oncogenic transcription factor <jats:italic><jats:styled-content style=\"fixed-case\">TAL<\/jats:styled-content>1<\/jats:italic>. Importantly, we examined the <jats:italic>in vivo<\/jats:italic> anti\u2010leukaemic efficacy of the clinical <jats:styled-content style=\"fixed-case\">SINE<\/jats:styled-content> compound <jats:styled-content style=\"fixed-case\">KPT<\/jats:styled-content>\u2010330 against T\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> and acute myeloid leukaemia (<jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>) cells. These studies demonstrated striking <jats:italic>in vivo<\/jats:italic> activity of <jats:styled-content style=\"fixed-case\">KPT<\/jats:styled-content>\u2010330 against <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> cells, with little toxicity to normal murine haematopoietic cells. Taken together, our results show that <jats:styled-content style=\"fixed-case\">SINE CRM<\/jats:styled-content>1 antagonists represent promising \u2018first\u2010in\u2010class\u2019 drugs with a novel mechanism of action and wide therapeutic index, and imply that drugs of this class show promise for the targeted therapy of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.12231","type":"journal-article","created":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T15:15:23Z","timestamp":1359990923000},"page":"117-127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":177,"title":["<scp>KPT<\/scp>\u2010330 inhibitor of <scp>CRM<\/scp>1 (<scp>XPO<\/scp>1)\u2010mediated nuclear export has selective anti\u2010leukaemic activity in preclinical models of <scp>T<\/scp>\u2010cell acute lymphoblastic leukaemia and acute myeloid leukaemia"],"prefix":"10.1111","volume":"161","author":[{"given":"Julia","family":"Etchin","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Boston MA USA"},{"name":"Division of Hematology\/Oncology Children's Hospital Boston, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi","family":"Sanda","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Boston MA USA"},{"name":"Division of Hematology\/Oncology Children's Hospital Boston, Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Boston MA USA"},{"name":"Division of 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