{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:46:30Z","timestamp":1790855190986,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","award":["INCa_15670"],"award-info":[{"award-number":["INCa_15670"]}],"id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) is a rare and aggressive hematological malignancy primarily affecting adolescents and young adults and is scarce in infants and toddlers under age 3. Unlike B\u2010ALL, T\u2010ALL in this young population remains poorly characterized due to limited data and lacks evidence\u2010based guidelines to help clinicians determine the optimal treatment approach. In this study, we conducted a comprehensive genetic analysis of infant\/toddler T\u2010ALL cases from a French national cohort, utilizing high\u2010throughput targeted sequencing, optical genome mapping, and RNA sequencing. Genetic analysis revealed the absence of\n                    <jats:italic>TLX1\/3<\/jats:italic>\n                    dysregulation. Instead, we identified a significant prevalence of\n                    <jats:italic>NKX2<\/jats:italic>\n                    rearrangements (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20099, 33%), co\u2010occurring with\n                    <jats:italic>MYB<\/jats:italic>\n                    alterations (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095\/9) or chromothripsis\u2010like events (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093\/9). Additional findings included\n                    <jats:italic>TAL1\/\u2010like<\/jats:italic>\n                    anomalies (30%),\n                    <jats:italic>STAG2::LMO2<\/jats:italic>\n                    (15%),\n                    <jats:italic>ETS<\/jats:italic>\n                    rearrangements (15%), and rarely,\n                    <jats:italic>KMT2A<\/jats:italic>\n                    rearrangements (7%). Comparative analyses with 245 patients aged 3\u201318 years, enrolled in the pediatric FRALLE2000T French protocol, underscored the distinct clinical and genetic profiles of infants\/toddlers. Despite presenting with higher rates of hyperleukocytosis and slower responses to treatment, they demonstrated comparable survival outcomes to older pediatric patients, with a 5\u2010year overall survival (OS) rate of 75.4% (95% confidence interval [CI]: 60.0%\u201394.8%) versus 75.2% (95% CI: 69.8%\u201381.1%),\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.86. Notably, alterations in\n                    <jats:italic>NKX2<\/jats:italic>\n                    ,\n                    <jats:italic>KMT2A<\/jats:italic>\n                    , and\n                    <jats:italic>STAG2::LMO2<\/jats:italic>\n                    delineated oncogenic subgroups exhibiting a remarkable 100% OS rate, while patients with\n                    <jats:italic>TAL1<\/jats:italic>\n                    or\n                    <jats:italic>ETS<\/jats:italic>\n                    dysregulation experienced less favorable outcomes. This was further supported by analyses of data from the COG AALL0434 trial, enhancing our understanding of T\u2010ALL in infants\/toddlers. Large\u2010scale collaborative studies remain essential to confirm these findings and refine treatment strategies.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70154","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T10:44:28Z","timestamp":1748342668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oncogenomic profiling in infant\u2013toddler T\u2010ALL identifies NKX2 family genes as drivers linked to favorable outcomes"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8440-7299","authenticated-orcid":false,"given":"Manon","family":"Delafoy","sequence":"first","affiliation":[{"name":"INSERM U1151, Institut Necker Enfants Malades (INEM) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Balducci","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology, Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0448-8811","authenticated-orcid":false,"given":"Mathieu","family":"Simonin","sequence":"additional","affiliation":[{"name":"INSERM U1151, Institut Necker Enfants Malades (INEM) Paris France"},{"name":"Department of Pediatric Hematology and Oncology AP\u2010HP, Armand Trousseau Hospital Sorbonne Universit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Pinton","sequence":"additional","affiliation":[{"name":"INSERM U1151, Institut Necker Enfants Malades (INEM) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Charbonnier","sequence":"additional","affiliation":[{"name":"INSERM U1151, Institut Necker Enfants Malades (INEM) Paris France"},{"name":"Laboratory of Onco\u2010Hematology, Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucien","family":"Courtois","sequence":"additional","affiliation":[{"name":"INSERM U1151, Institut Necker Enfants Malades (INEM) Paris France"},{"name":"Laboratory of Onco\u2010Hematology, Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"INSERM U1151, Institut Necker Enfants Malades (INEM) Paris France"},{"name":"Laboratory of Onco\u2010Hematology, Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP) Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Gillet","sequence":"additional","affiliation":[{"name":"INSERM 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Simon","family":"Rohrlich","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Nice Universit\u00e9 de C\u00f4te d'Azur Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Bodet","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology University Hospital of Caen Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Grardel","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology Centre Hospitalier R\u00e9gional Universitaire (CHRU) Lille, U1172, INSERM Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Lubnau","sequence":"additional","affiliation":[{"name":"Pediatric Onco\u2010Hematology Department Nancy University Hospital Vandoeuvre\u2010l\u00e8s\u2010Nancy 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