{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:39:46Z","timestamp":1773005986627,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018675","name":"Kids' Cancer Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018675","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":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) is a biologically heterogeneous and clinically aggressive malignancy, where outcomes remain poor for patients with early relapse or refractory disease. Although tyrosine kinase alterations represent potentially actionable lesions, understanding of their functional and therapeutic relevance in T\u2010ALL is limited. Here, we report the first case of an\n                    <jats:italic>IRF2BP2::JAK2<\/jats:italic>\n                    fusion in a pediatric patient with high\u2010risk T\u2010ALL, identified through whole\u2010genome and transcriptome sequencing. Using CRISPR\u2010Cas9 genome engineering, we modeled the\n                    <jats:italic>Irf2bp2::Jak2<\/jats:italic>\n                    fusion in Ba\/F3 cells and showed that it confers cytokine\u2010independent growth, localizes to the cytoplasm, and drives constitutive JAK\u2013STAT signaling. Importantly, both type I (ruxolitinib) and type II (CHZ868) JAK inhibitors potently inhibited the fusion. These findings establish\n                    <jats:italic>IRF2BP2::JAK2<\/jats:italic>\n                    as a novel oncogenic driver and druggable vulnerability in T\u2010ALL and represent the first reported instance of an\n                    <jats:italic>IRF2BP2<\/jats:italic>\n                    fusion directly activating a non\u2010receptor tyrosine kinase. More broadly, this work underscores the critical role of functional modeling in defining the biological and therapeutic significance of rare genomic alterations to enable the translation of precision medicine to the clinic.\n                  <\/jats:p>","DOI":"10.1002\/gcc.70112","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:21:48Z","timestamp":1771500108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>IRF2BP2::JAK2<\/i>\n                    Defines a Novel Kinase\u2010Activating Fusion in Pediatric T\u2010Cell Acute Lymphoblastic Leukemia"],"prefix":"10.1002","volume":"65","author":[{"given":"Fatimah B.","family":"Jalud","sequence":"first","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tasnia","family":"Ibnat","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlyn","family":"Kew","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg Melbourne Australia"},{"name":"School of Cancer Medicine La Trobe University  Bundoora Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine UNSW Sydney  Kensington New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Dias","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsea","family":"Mayoh","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine UNSW Sydney  Kensington New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0428-6195","authenticated-orcid":false,"given":"Hansen J.","family":"Kosasih","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine UNSW Sydney  Kensington New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0837-1231","authenticated-orcid":false,"given":"Daniel","family":"Thomas","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute  Adelaide Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loretta M. S.","family":"Lau","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine UNSW Sydney  Kensington New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Hanna","sequence":"additional","affiliation":[{"name":"Children's Cancer Centre Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0740-3606","authenticated-orcid":false,"given":"Bhavna","family":"Padhye","sequence":"additional","affiliation":[{"name":"Department of Oncology Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E.","family":"de Bock","sequence":"additional","affiliation":[{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine UNSW Sydney  Kensington New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-8617","authenticated-orcid":false,"given":"Paul G.","family":"Ekert","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre  Parkville Victoria Australia"},{"name":"Children's Cancer Institute, Lowy Cancer Research Centre UNSW Sydney  Sydney New South Wales Australia"},{"name":"School of Clinical Medicine UNSW Sydney  Kensington New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-9580","authenticated-orcid":false,"given":"Teresa","family":"Sadras","sequence":"additional","affiliation":[{"name":"Olivia Newton\u2010John Cancer Research Institute  Heidelberg Melbourne Australia"},{"name":"School of Cancer Medicine La Trobe University  Bundoora Melbourne Australia"},{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"The Sir Peter MacCallum Department of Oncology University of Melbourne  Parkville Victoria 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