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Despite this, data from adult T\u2010ALL patients treated with specific chemotherapeutic regimens that examine predictive markers and describe relapse mechanisms are scarce. In this study, we studied 74 paired diagnosis\u2010relapse samples from 37 patients homogeneously treated with three consecutive measurable residual disease\u2010oriented trials to identify genetic determinants involved in relapse in adult T\u2010ALL. Analysis of single\u2010nucleotide variants and copy number alterations consistently found\n                    <jats:italic>N\/KRAS<\/jats:italic>\n                    mutations (20% relapsed cases) at diagnosis and at relapse (resistance profile).\n                    <jats:italic>N\/KRAS<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>mut<\/jats:italic>\n                    <\/jats:sup>\n                    patients frequently relapse early during consolidation treatment. Relapse\u2010specific mutations in\n                    <jats:italic>NT5C2, NR3C1<\/jats:italic>\n                    ,\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    , and\n                    <jats:italic>TP53<\/jats:italic>\n                    (40% relapse cases) were not detected at diagnosis by conventional molecular techniques (relapse profile). However, single\u2010cell\u2010based analysis revealed a very minor clone containing the NT5C2(p.R367Q) variant at diagnosis. Patients with the NT5C2(p.R367Q) variant mostly relapse later during maintenance treatment. Tracking the\n                    <jats:italic>NT5C2<\/jats:italic>\n                    variant by digital PCR confirm the expansion of the NT5C2 clone at maintenance treatment. Overall, our exploratory analysis suggests a role for these genetic events, most of which have already been described in pediatric cases, driving resistance associated to specific chemotherapeutic agents, contributing to the relapse of a high proportion of adult T\u2010ALL patients (60%).\n                  <\/jats:p>","DOI":"10.1002\/hem3.70148","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T05:51:26Z","timestamp":1748238686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic evolution and relapse\u2010associated mutations in adult T\u2010cell acute lymphoblastic leukemia patients treated in PETHEMA trials"],"prefix":"10.1002","volume":"9","author":[{"given":"Celia","family":"Gonz\u00e1lez\u2010Gil","sequence":"first","affiliation":[{"name":"Institut d'Investigaci\u00f3 contra la Leucemia Josep Carreras (IJC), Campus ICO\u2010Germans Trias i Pujol Universitat 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