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In T-cell acute lymphoblastic leukemia (T-ALL), their incidence and prognostic implications remain poorly reported. Our targeted next-generation sequencing approach allowed comprehensive assessment of genotype across the entire <jats:italic>IDH1<\/jats:italic> and <jats:italic>IDH2<\/jats:italic> locus in 1085 consecutive unselected and newly diagnosed patients with T-ALL and identified 4% of, virtually exclusive (47 of 49 patients), <jats:italic>IDH1\/2<\/jats:italic><jats:sup>Mut<\/jats:sup>. Mutational patterns of <jats:italic>IDH1\/2<\/jats:italic><jats:sup>Mut<\/jats:sup> in T-ALL present some specific features compared to AML. Whereas <jats:italic>IDH2<\/jats:italic><jats:sup>R140Q<\/jats:sup> mutation was frequent in T-ALL (25 of 51 mutations), the <jats:italic>IDH2<\/jats:italic><jats:sup>R172<\/jats:sup> AML hotspot was absent. <jats:italic>IDH2<\/jats:italic> mutations were associated with older age, an immature phenotype, more frequent <jats:italic>RAS<\/jats:italic> gain-of-function mutations and epigenetic regulator loss-of-function alterations (<jats:italic>DNMT3A<\/jats:italic> and <jats:italic>TET2<\/jats:italic>). <jats:italic>IDH2<\/jats:italic> mutations, contrary to <jats:italic>IDH1<\/jats:italic> mutations, appeared to be an independent prognostic factor in multivariate analysis with the <jats:italic>NOTCH1\/FBXW7\/RAS\/PTEN<\/jats:italic> classifier. <jats:italic>IDH2<\/jats:italic><jats:sup>Mut<\/jats:sup> were significantly associated with a high cumulative incidence of relapse and very dismal outcome, suggesting that <jats:italic>IDH2<\/jats:italic>-mutated T-ALL cases should be identified at diagnosis in order to benefit from therapeutic intensification and\/or specific <jats:italic>IDH2<\/jats:italic> inhibitors.<\/jats:p>","DOI":"10.1186\/s13045-021-01068-4","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T10:03:10Z","timestamp":1620036190000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL"],"prefix":"10.1186","volume":"14","author":[{"given":"Mathieu","family":"Simonin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Bontoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-\u00c9milie","family":"Dourthe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Lenglin\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume P.","family":"Andrieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Lhermitte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Graux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Grardel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Cayuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Huguet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Arnoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Ducassou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Macintyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Gandemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Dombret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Ifrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Baruchel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Boissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Asnafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"1068_CR1","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1056\/NEJMra1400972","volume":"373","author":"SP Hunger","year":"2015","unstructured":"Hunger SP, Mullighan CG. 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