{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:24:06Z","timestamp":1779888246372,"version":"3.53.1"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2025,12]]},"abstract":"Abstract<\/jats:title>\n \n The T\u2010cell Leukemia Homeobox 1 (\n TLX1<\/jats:italic>\n ) oncogene is frequently deregulated in T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) and T\u2010cell lymphoblastic lymphoma (T\u2010LBL). In most instances,\n TLX1<\/jats:italic>\n overexpression results from its juxtaposition with a T\u2010cell receptor (\n TCR<\/jats:italic>\n ) locus caused by interchromosomal translocations. However, in the subset of non\u2010\n TCR<\/jats:italic>\n \u2010translocated\n TLX1<\/jats:italic>\n \u2010positive (non\u2010\n TCR TLX1<\/jats:italic>\n +) T\u2010ALL cases, the underlying mechanisms driving\n TLX1<\/jats:italic>\n overexpression and their clinico\u2010biological implications remain unclear. By integrating high\u2010resolution data from next\u2010generation sequencing, fluorescence in situ hybridization, karyotyping, optical genome mapping, and long\u2010read whole\u2010genome sequencing across a cohort of 1122 adult and pediatric T\u2010ALL\/T\u2010LBL cases, we identified\n TLX1<\/jats:italic>\n overexpression in 11% of T\u2010ALL\/T\u2010LBL cases, with an unexpected 14% incidence of non\u2010\n TCR TLX1<\/jats:italic>\n + cases among\n TLX1<\/jats:italic>\n + cases. Non\u2010\n TCR TLX1<\/jats:italic>\n \u2009+\u2009T\u2010ALL cases show distinct clinico\u2010biological features, including a lower frequency of cortical phenotype compared to the\n TCR<\/jats:italic>\n \u2010translocated\n TLX1<\/jats:italic>\n + (\n TCR TLX1<\/jats:italic>\n +) subgroup, regardless of\n TLX1<\/jats:italic>\n expression levels. In non\u2010\n TCR TLX1<\/jats:italic>\n \u207a cases,\n TLX1<\/jats:italic>\n deregulation results mostly (83%) from the hijacking of the\n ANKRD1<\/jats:italic>\n and\n PCGF5<\/jats:italic>\n enhancer at 10q23.31 through various chromosomal aberrations. Genomic analyses revealed that these aberrations juxtapose the\n ANKRD1<\/jats:italic>\n and\n PCGF5<\/jats:italic>\n enhancer with\n TLX1<\/jats:italic>\n , driving its overexpression. Importantly, survival analysis revealed that non\u2010\n TCR TLX1<\/jats:italic>\n + patients had significantly poorer outcomes compared to their\n TCR TLX1<\/jats:italic>\n \u207a counterparts (3y\u2010OS: 55% vs. 90%,\n P<\/jats:italic>\n \u2009<\u20090.001 and 3y\u2010DFS: 45% vs. 75%,\n P<\/jats:italic>\n \u2009=\u20090.02). These findings, consistent with our previous observations in\n TAL1<\/jats:italic>\n \u2010driven T\u2010ALL, confirm that the clinico\u2010biological impact of an oncogene is influenced by the specific mechanism underlying its deregulation.\n <\/jats:p>","DOI":"10.1002\/hem3.70281","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T02:55:50Z","timestamp":1766976950000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TLX1 translocation variants and enhancer hijacking influence clinical outcome in T\u2010cell acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6792-1291","authenticated-orcid":false,"given":"Estelle","family":"Balducci","sequence":"first","affiliation":[{"name":"Laboratoire d'Onco\u2010H\u00e9matologie, H\u00f4pital Necker\u2010Enfants Malades Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) 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