{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:06:20Z","timestamp":1789369580768,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T00:00:00Z","timestamp":1484697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000402","name":"Kay Kendall Leukaemia Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000402","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007903","name":"Bloodwise","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deregulated expression of the type I cytokine receptor, <jats:italic>CRLF2<\/jats:italic>, is observed in 5\u201315% of precursor B\u2010cell acute lymphoblastic leukaemia (B\u2010ALL). We aimed to determine the clinical and genetic landscape of those with <jats:italic>IGH\u2010CRLF2<\/jats:italic> or <jats:italic>P2RY8\u2010CRLF2<\/jats:italic> (<jats:italic>CRLF2<\/jats:italic>\u2010r) using multiple genomic approaches. Clinical and demographic features of <jats:italic>CRLF2<\/jats:italic>\u2010r patients were characteristic of B\u2010ALL. Patients with <jats:italic>IGH\u2010CRLF2<\/jats:italic> were older (14 y vs. 4 y, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), while the incidence of <jats:italic>CRLF2<\/jats:italic>\u2010r among Down syndrome patients was high (50\/161, 31%). <jats:italic>CRLF2<\/jats:italic>\u2010r co\u2010occurred with primary chromosomal rearrangements but the majority (111\/161, 69%) had B\u2010other ALL. Copy number alteration (CNA) profiles were similar to B\u2010other ALL, although <jats:italic>CRLF2<\/jats:italic>\u2010r patients harbored higher frequencies of <jats:italic>IKZF1<\/jats:italic> (60\/138, 43% vs. 77\/1351, 24%) and <jats:italic>BTG1<\/jats:italic> deletions (20\/138, 15% vs. 3\/1351, 1%). There were significant differences in CNA profiles between <jats:italic>IGH\u2010CRLF2<\/jats:italic> and <jats:italic>P2RY8\u2010CRLF2<\/jats:italic> patients: <jats:italic>IKZF1<\/jats:italic> (25\/35, 71% vs. 36\/108, 33%, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), <jats:italic>BTG1<\/jats:italic> (11\/35, 31% vs. 10\/108, 9%, <jats:italic>P<\/jats:italic> =.004), and <jats:italic>ADD3<\/jats:italic> deletions (9\/19, 47% vs. 5\/38, 13%, <jats:italic>P<\/jats:italic> =.008). A novel gene fusion, <jats:italic>USP9X\u2010DDX3X<\/jats:italic>, was discovered in 10\/54 (19%) of patients. Pathway analysis of the mutational profile revealed novel involvement for focal adhesion. Although the functional relevance of many of these abnormalities are unknown, they likely activate additional pathways, which may represent novel therapeutic targets.<\/jats:p>","DOI":"10.1002\/gcc.22439","type":"journal-article","created":{"date-parts":[[2016,12,29]],"date-time":"2016-12-29T23:13:10Z","timestamp":1483053190000},"page":"363-372","source":"Crossref","is-referenced-by-count":60,"title":["Characterisation of the genomic landscape of <i>CRLF2<\/i>\u2010rearranged acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"56","author":[{"given":"Lisa J.","family":"Russell","sequence":"first","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Jones","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Enshaei","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Tonin","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra L.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyanthy","family":"Eswaran","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirintra","family":"Nakjang","sequence":"additional","affiliation":[{"name":"Bioinformatics Support Unit, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elli","family":"Papaemmanuil","sequence":"additional","affiliation":[{"name":"Department of Epidemiology\u2010Biostatistics Memorial Sloan Kettering Cancer Center  USA"},{"name":"Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M. C.","family":"Tubio","sequence":"additional","affiliation":[{"name":"Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele K.","family":"Fielding","sequence":"additional","affiliation":[{"name":"Research Department of Haemaoloty UCL Cancer Institute London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Vora","sequence":"additional","affiliation":[{"name":"Department of Haematology Sheffield Children's Hospital Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony V.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-6794","authenticated-orcid":false,"given":"Christine J.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2012.01.001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70339-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808253"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1403088"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-208397"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.51.3242"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.469"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22190"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-394221"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-245944"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2011.01319.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-443218"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.84"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.40.3907"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20818"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110580"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.005"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.4105"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-297135"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-562918"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.085175"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.103820"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2874"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.024"},{"key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/0471250953.bi1507s52","article-title":"cgpPindel: identifying somatically acquired insertion and deletion events from paired end sequencing","volume":"52","author":"Raine KM","year":"2015","journal-title":"Curr Protoc Bioinformatics."},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-170928"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-670166"},{"key":"e_1_2_6_32_1","article-title":"Use of minimal residual disease assessment to redefine induction failure in pediatric acute lymphoblastic leukemia","author":"O'Connor D","journal-title":"J Clin Oncol"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830450118"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-389932"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.80"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3230"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2532"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3301"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.101725"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.29182"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13211"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1960"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11213"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11378"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.281"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.02.115"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-415448"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.06.005"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0647"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0029(20001101)51:3<280::AID-JEMT7>3.0.CO;2-O"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201501025"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500331200"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.07.016"},{"key":"e_1_2_6_55_1","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1182\/blood.V126.23.3766.3766","article-title":"Efficacy of Focal Adhesion Kinase Inhibition in Combination with Dasatinib in BCR\u2010ABL1 Acute Lymphoblastic Leukemia","volume":"126","author":"Churchman ML","year":"2015","journal-title":"Blood."}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.22439","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.22439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:25:44Z","timestamp":1696602344000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.22439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,18]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/gcc.22439"],"URL":"https:\/\/doi.org\/10.1002\/gcc.22439","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,18]]}}}