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Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>), a common B cell malignancy with heterogeneous outcomes. We previously demonstrated that differences in the amount of <jats:styled-content style=\"fixed-case\">SET<\/jats:styled-content> oncoprotein (a physiological inhibitor of the serine\/threonine phosphatase, <jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>2A) is associated with clinical aggressiveness in patients with <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>. It is unknown if alternative splicing of gene transcripts regulating kinases and phosphatases affects disease pathobiology and <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> progression. We show here for the first time that <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of the alternatively spliced <jats:styled-content style=\"fixed-case\">SET<\/jats:styled-content> isoforms, <jats:italic><jats:styled-content style=\"fixed-case\">SETA<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">SETB<\/jats:styled-content><\/jats:italic> (<jats:styled-content style=\"fixed-case\">SET<\/jats:styled-content>\u03b1 and <jats:styled-content style=\"fixed-case\">SET<\/jats:styled-content>\u03b2), significantly correlate with disease severity (overall survival and time\u2010to\u2010first\u2010treatment) in <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patients. In addition, we demonstrate that relative increase of <jats:italic><jats:styled-content style=\"fixed-case\">SETA<\/jats:styled-content><\/jats:italic> to <jats:italic><jats:styled-content style=\"fixed-case\">SETB<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> can discriminate patients with a more aggressive disease course within the otherwise favourable <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> risk classifications of <jats:italic><jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content><\/jats:italic> mutated and favourable hierarchical fluorescence <jats:italic>in\u00a0situ<\/jats:italic> hybridisation groups. We validate our finding by showing comparable relationships of <jats:italic><jats:styled-content style=\"fixed-case\">SET<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> with disease outcomes using samples from an independent <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cohort from a separate institution. These findings indicate that alternative splicing of <jats:italic><jats:styled-content style=\"fixed-case\">SET<\/jats:styled-content><\/jats:italic>, and potentially other signalling cascade molecules, influences <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> biology and patient outcomes.<\/jats:p>","DOI":"10.1111\/bjh.15677","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T01:04:20Z","timestamp":1542330260000},"page":"605-615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>SET<\/scp> alpha and <scp>SET<\/scp> beta <scp>mRNA<\/scp> isoforms in chronic lymphocytic leukaemia"],"prefix":"10.1111","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-2807","authenticated-orcid":false,"given":"Danielle M.","family":"Brander","sequence":"first","affiliation":[{"name":"Duke University Medical Center Durham NC USA"},{"name":"Duke Cancer Institute Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2938-5704","authenticated-orcid":false,"given":"Daphne R.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"},{"name":"Duke Cancer Institute Durham NC USA"},{"name":"Durham VA Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia D.","family":"Volkheimer","sequence":"additional","affiliation":[{"name":"Durham VA Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale J.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Z.","family":"Rassenti","sequence":"additional","affiliation":[{"name":"University of California San Diego Moores Cancer Center San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kipps","sequence":"additional","affiliation":[{"name":"University of California San Diego Moores Cancer Center San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eross","family":"Guadalupe","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dadong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"},{"name":"Duke Cancer Institute Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"},{"name":"Duke Cancer Institute Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter","family":"Davis","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouros","family":"Owzar","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham NC USA"},{"name":"Duke Cancer Institute Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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