{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:27:43Z","timestamp":1789720063089,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023181","name":"Agencja Bada\u0144 Medycznych","doi-asserted-by":"publisher","award":["2019\/ABM\/01\/00069"],"award-info":[{"award-number":["2019\/ABM\/01\/00069"]}],"id":[{"id":"10.13039\/501100023181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023181","name":"Agencja Bada\u0144 Medycznych","doi-asserted-by":"publisher","award":["2024\/ABM\/03\/KPO\/KPOD.07.07\u2010IW.07\u201000156\/24\u201000"],"award-info":[{"award-number":["2024\/ABM\/03\/KPO\/KPOD.07.07\u2010IW.07\u201000156\/24\u201000"]}],"id":[{"id":"10.13039\/501100023181","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>B\u2010cell precursor acute lymphoblastic leukemia (BCP\u2010ALL) with the t(5;14)(q31;q32) chromosomal translocation resulting in an <jats:italic>IGH<\/jats:italic>::<jats:italic>IL3<\/jats:italic> fusion is an exceptionally rare lymphoid malignancy presenting with hypereosinophilia. Germline <jats:italic>PAX5<\/jats:italic> alterations, including sequence variants and deletions, are associated with a selective susceptibility to BCP\u2010ALL and lymphomas, based on a limited number of affected families worldwide. Here, we report a 6\u2010year\u2010old male with BCP\u2010ALL with the t(5;14)(q31;q32) translocation and harboring a novel constitutional <jats:italic>PAX5<\/jats:italic> variant (NM_016734.3:c.[295dup];[=], p.[(Ile99Asnfs*3)];[(=)]). Despite the low representation of the leukemic clone in the bone marrow, the <jats:italic>IGH::IL3<\/jats:italic> fusion was identified by both fluorescent in\u00a0situ hybridization (FISH) and optical genome mapping (OGM). Although hypereosinophilia poses a risk of multiorgan damage, our patient exhibited only pneumonia and asymptomatic neuroimaging alterations in the central nervous system. The patient achieved remission by the end of induction and is currently continuing maintenance therapy. In line with existing literature, familial segregation of the <jats:italic>PAX5<\/jats:italic> variant demonstrated high but incomplete penetrance, as two leukemia\u2010free mutation carriers displayed only subclinical B lymphocyte maturation abnormalities without hypogammaglobulinemia. Our report underscores the diagnostic utility of OGM, which unequivocally demonstrated the characteristic translocation. Typically, BCP\u2010ALL in affected family members exhibits secondary somatic aberrations involving the wild\u2010type <jats:italic>PAX5<\/jats:italic> allele, including structural variants or loss of heterozygosity (LOH) of chromosome 9p, as well as <jats:italic>PAX5<\/jats:italic> somatic mutations. To our knowledge, this is the first human report aligning with animal models, which suggests that secondary alterations activating the JAK\u2013STAT pathway may potentially contribute to leukemogenesis in a <jats:italic>PAX5<\/jats:italic> mutation background.<\/jats:p>","DOI":"10.1002\/gcc.70080","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:39:44Z","timestamp":1758544784000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp><i>IGH<\/i><\/scp>::<scp><i>IL3<\/i><\/scp>\u2010Rearranged B\u2010Cell Precursor Acute Lymphoblastic Leukemia With Hypereosinophilia in a Child With a Novel <scp><i>PAX5<\/i><\/scp> Germline Variant"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5399-4703","authenticated-orcid":false,"given":"Bartosz","family":"Urba\u0144ski","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-8842","authenticated-orcid":false,"given":"Karolina","family":"Miarka\u2010Walczyk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology Medical University of Lodz  Lodz Poland"},{"name":"Department of Genetic Predisposition to Cancer Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-6627","authenticated-orcid":false,"given":"Zuzanna","family":"Urba\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology Medical University of Lodz  Lodz Poland"},{"name":"Department of Genetic Predisposition to Cancer Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"W\u0105sikowska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3912-7143","authenticated-orcid":false,"given":"El\u017cbieta","family":"Sa\u0142aci\u0144ska\u2010\u0141o\u015b","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Oncology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-439X","authenticated-orcid":false,"given":"Karolina","family":"Bukowska\u2010Strakova","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transplantology, Institute of Pediatrics Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-0775","authenticated-orcid":false,"given":"Monika","family":"Lejman","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Diagnostics Medical University of Lublin  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Jaroszek","sequence":"additional","affiliation":[{"name":"Histocompatibility Laboratory Children's Memorial Health Institute  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8949-047X","authenticated-orcid":false,"given":"Barbara","family":"Pi\u0105tosa","sequence":"additional","affiliation":[{"name":"Histocompatibility Laboratory Children's Memorial Health Institute  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-5851","authenticated-orcid":false,"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3089-6947","authenticated-orcid":false,"given":"Agata","family":"Pastorczak","sequence":"additional","affiliation":[{"name":"Department of Genetic Predisposition to Cancer Medical University of Lodz  Lodz Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-6969","authenticated-orcid":false,"given":"Szymon","family":"Janczar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology Medical University of Lodz  Lodz 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