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Relapse remains associated with limited curative options. Frontline treatment is largely extrapolated from T\u2010cell acute lymphoblastic leukemia (T\u2010ALL) treatment, reflecting the ongoing debate, whether both entities represent distinct diseases or variants within one spectrum. This review focuses on T\u2010LBL, summarizing shared and distinct clinical, pathological, and biological features in comparison to T\u2010ALL. We address diagnostic and staging challenges, and current limitations of clinical risk stratification. Biomarkers, such as genetic variants in\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    \/\n                    <jats:italic>FBXW7<\/jats:italic>\n                    , are discussed in the context of dynamic risk assessment. Particularly emphasizing the molecular landscape of T\u2010LBL and recurrent pathway alterations.\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    emerges as central determinant of disease biology. Activating\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    mutations (NOTCH1\n                    <jats:italic>\n                      <jats:sup>mut<\/jats:sup>\n                    <\/jats:italic>\n                    ) are frequently associated with favorable outcomes and used for risk stratification in the ongoing trial LBL 2018 (EUCT number: 2023\u2010508101\u201024\u201000).\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    fusions resulting in excessive\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    signaling are associated with increased relapse incidences, suggesting that the intracellular amount of\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    differentiates between tumor suppressive versus tumor supportive activity. These findings are placed in the context of recently described\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    variants in T\u2010ALL, reported to similarly cause aberrant\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    activation. Future studies may consider incorporating detailed\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    status to understand disease dynamics and enhance therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/1545-5017.70380","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:40:05Z","timestamp":1778222405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two Faces of\n                    <i>NOTCH1<\/i>\n                    in Childhood Lymphoblastic T\u2010Cell Neoplasia: Prognostic Divergence of Mutational and Structural Aberrations"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7168-9423","authenticated-orcid":false,"given":"Marie C.","family":"Heider","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology and Non\u2010Hodgkin Lymphoma Berlin\u2010Frankfurt\u2010Muenster Study Center University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Alfert","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology and Non\u2010Hodgkin Lymphoma Berlin\u2010Frankfurt\u2010Muenster Study Center University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Hotfilder","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology and Non\u2010Hodgkin Lymphoma Berlin\u2010Frankfurt\u2010Muenster Study Center University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Burkardt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology and Non\u2010Hodgkin Lymphoma Berlin\u2010Frankfurt\u2010Muenster Study Center University Hospital Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0864-1585","authenticated-orcid":false,"given":"Marcel","family":"te Vrugt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology and Non\u2010Hodgkin Lymphoma Berlin\u2010Frankfurt\u2010Muenster Study Center University Hospital Muenster  Muenster 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