{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:21:14Z","timestamp":1793830874993,"version":"4.6.1"},"reference-count":27,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>We previously reported a better outcome in adult and pediatric T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and\/or FBXW7 mutations without alterations of K-N-RAS and PTEN genes. Availability of high-throughput next-generation sequencing (NGS) strategies led us to refine the outcome prediction in T-ALL. Targeted whole-exome sequencing of 72 T-ALL\u2013related oncogenes was performed in 198 adults with T-ALLs in first remission from the GRAALL-2003\/2005 protocols and 242 pediatric patients with T-ALLs from the FRALLE2000T. This approach enabled the identification of, to our knowledge, the first NGS-based classifier in T-ALL, categorizing low-risk patients as those with N\/F, PHF6, or EP300 mutations, excluding N-K-RAS, PI3K pathway (PTEN, PIK3CA, and PIK3R1), TP53, DNMT3A, IDH1\/2, and IKZF1 alterations, with a 5-year cumulative incidence of relapse (CIR) estimated at 21%. Conversely, the remaining patients were classified as high risk, exhibiting a 5-year CIR estimated at 47%. We externally validated this stratification in the pediatric cohort. NGS-based classifier was highly prognostic independently of minimal residual disease (MRD) and white blood cell (WBC) counts, in both adult and pediatric cohorts. Integration of the NGS-based classifier into a comprehensive risk-stratification model, including WBC count at diagnosis and MRD at the end of induction, enabled the identification of an adverse-risk subgroup (25%) with a 5-year CIR estimated at 51%, and a favorable-risk group (32%) with a 5-year CIR estimated at 12%. NGS-based stratification combined with WBC and MRD sharpens the prognostic classification in T-ALL and identifies a new subgroup of patients who may benefit from innovative therapeutic approaches. The GRAALL-2003\/2005 studies were registered at www.ClinicalTrials.gov as #NCT00222027 and #NCT00327678.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023023754","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T16:04:38Z","timestamp":1717776278000},"page":"1570-1580","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":50,"title":["NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0448-8811","authenticated-orcid":false,"given":"Mathieu","family":"Simonin","sequence":"first","affiliation":[{"name":"1Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"2Institut Necker-Enfants Malades, INSERM U1151, Paris, France"},{"name":"3Department of Pediatric Hematology and Oncology, Armand Trousseau Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-0477","authenticated-orcid":false,"given":"Lo\u00efc","family":"Vasseur","sequence":"additional","affiliation":[{"name":"4Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation, INSERM U1153, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"5Adolescent and Young Adult Hematology Unit, Saint Louis University Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Lenglin\u00e9","sequence":"additional","affiliation":[{"name":"6Institut de Recherche Saint-Louis, EA-3518, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"7Department of Hematology, Saint Louis University Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"1Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"2Institut Necker-Enfants Malades, INSERM U1151, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Cabannes-Hamy","sequence":"additional","affiliation":[{"name":"8Department of Hematology, Versailles Hospital, Le Chesnay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Balsat","sequence":"additional","affiliation":[{"name":"9Clinical Hematology Department, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-B\u00e9nite, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Touzart","sequence":"additional","affiliation":[{"name":"1Laboratory of Onco-Hematology, Necker-Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"2Institut Necker-Enfants Malades, INSERM U1151, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9236-3623","authenticated-orcid":false,"given":"Carlos","family":"Graux","sequence":"additional","affiliation":[{"name":"13Department of Hematology, Universit\u00e9 Catholique de Louvain, CHU UCL Namur\u2013site Godinne, Yvoir, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-1312","authenticated-orcid":false,"given":"Nathalie","family":"Grardel","sequence":"additional","affiliation":[{"name":"14Department of Hematology, University Hospital Claude Huriez, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Cayuela","sequence":"additional","affiliation":[{"name":"6Institut de Recherche Saint-Louis, EA-3518, Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"15Laboratory of Hematology, Saint Louis University Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Arnoux","sequence":"additional","affiliation":[{"name":"16Laboratory of Hematology, La Timone University Hospital, Assitance Publique des H\u00f4pitaux de Marseille, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-233X","authenticated-orcid":false,"given":"Virginie","family":"Gandemer","sequence":"additional","affiliation":[{"name":"17Department of Pediatric Hematology and Oncology, University Hospital of Rennes, Rennes, 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