{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:06:00Z","timestamp":1790899560824,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>PAX5 is a member of the paired box (PAX) family of transcription factors involved in B\u2010cell development. <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup> has recently been described as a distinct genetic B\u2010cell precursor (BCP) acute lymphoblastic leukemia (ALL) subtype with a favorable prognosis in adults. In contrast, an unfavorable outcome has been observed in children. Our aim was to determine the frequency of <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup> in childhood BCP\u2010ALL treated according to the Associazione Italiana Ematologia ed Oncologia Pediatrica\u2010Berlin\u2010Frankfurt\u2010Muenster (AIEOP\u2010BFM) ALL 2000 protocol and to evaluate its clinical significance within this study cohort. The analyses included 1237 patients with ALL treated in the AIEOP\u2010BFM ALL 2000 trial with complete information for copy number variations (CNVs) of <jats:italic>IKZF1<\/jats:italic>, <jats:italic>PAX5<\/jats:italic>, <jats:italic>ETV6<\/jats:italic>, <jats:italic>RB1<\/jats:italic>, <jats:italic>BTG1<\/jats:italic>, <jats:italic>EBF1<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>CDKN2B,<\/jats:italic> and <jats:italic>ERG<\/jats:italic>. A customized TaqMan genotyping assay was used to screen for <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>. Sanger sequencing was used to confirm <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>\u2010positive results as well as to screen for second variants in <jats:italic>PAX5<\/jats:italic>. Agilent CGH\u2009+\u2009SNP arrays (e\u2010Array design 85\u2009320; Agilent Technologies) were performed in <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>\u2010positive patients to verify additional CNVs. Almost 2% (20\/1028) of our BCP\u2010ALL cohort were <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>\u2010positive. White blood cell counts higher than 50\u2009000\/\u03bcl as well as male sex were significantly (<jats:italic>P<\/jats:italic> &lt; .05) associated with <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>. Most of the <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>\u2010positive cases were 10\u2009years of age or older. <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>\u2010positive samples were enriched for deletions affecting <jats:italic>PAX5<\/jats:italic>, <jats:italic>IKZF1<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, and <jats:italic>CDKN2B<\/jats:italic>. Compared to <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup><jats:italic>\u2010<\/jats:italic>wildtype BCP\u2010ALL, <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup>\u2010positive patients showed a significantly reduced 5\u2010year overall survival (<jats:italic>P<\/jats:italic> = .042). Further studies should evaluate the interaction of <jats:italic>PAX5<\/jats:italic><jats:sup>P80R<\/jats:sup> with other genetic aberrations to further stratify intermediate risk pediatric BCP\u2010ALL.<\/jats:p>","DOI":"10.1002\/gcc.22882","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T10:54:09Z","timestamp":1593255249000},"page":"667-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Frequency and prognostic impact of <scp><i>PAX5<\/i><\/scp> p.<scp>P80R<\/scp> in pediatric acute lymphoblastic leukemia patients treated on an <scp>AIEOP\u2010BFM<\/scp> acute lymphoblastic leukemia protocol"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0728-8695","authenticated-orcid":false,"given":"Mareike","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5878-0546","authenticated-orcid":false,"given":"Maximilian","family":"Schieck","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Tauscher","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Lentes","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School  Hannover 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