2026-04-17T03:31:29Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/135292025-10-24T10:30:31Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Rodríguez Medina, Carlos author Hermosín, Lourdes author GONZÁLEZ GIL, CELIA author Morgades, Mireia author Fuster-Tormo, Francisco author Montesinos, Pau author Barba, Pere author 2025-08-12T08:31:49Z 2025-08-12T08:31:49Z 2025-05 Mutations; Relapse; T-cell acute lymphoblastic leukemia Mutacions; Recaiguda; Leucèmia limfoblàstica aguda de cèl·lules T Mutaciones; Recaída; Leucemia linfoblástica aguda de células T Relapse is the main cause of treatment failure in T-cell acute lymphoblastic leukemia (T-ALL). Despite this, data from adult T-ALL patients treated with specific chemotherapeutic regimens that examine predictive markers and describe relapse mechanisms are scarce. In this study, we studied 74 paired diagnosis-relapse samples from 37 patients homogeneously treated with three consecutive measurable residual disease-oriented trials to identify genetic determinants involved in relapse in adult T-ALL. Analysis of single-nucleotide variants and copy number alterations consistently found N/KRAS mutations (20% relapsed cases) at diagnosis and at relapse (resistance profile). N/KRAS mut patients frequently relapse early during consolidation treatment. Relapse-specific mutations in NT5C2, NR3C1, SMARCA4, and TP53 (40% relapse cases) were not detected at diagnosis by conventional molecular techniques (relapse profile). However, single-cell-based 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 NT5C2 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-ALL patients (60%). This project was supported by the AECC (GC16173697BIGA), ISCIII (PI19/01828, PI19/01183, and PI22/01880), co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future,” and CERCA/Generalitat de Catalunya SGR 2021 (ref 00560). Thaysa Lopes was supported by the Leukemia Stiftung (DJCLS 08R/2022). http://hdl.handle.net/11351/13529 Cèl·lules T Anomalies cromosòmiques Leucèmia limfoblàstica - Aspectes genètics Leucèmia limfoblàstica - Recaiguda PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation DISEASES::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma::Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Other subheadings::Other subheadings::Other subheadings::/genetics DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Treatment Failure FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación ENFERMEDADES::neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia-linfoma linfoblástico de células precursoras::leucemia-linfoma linfoblástico de células T precursoras Otros calificadores::Otros calificadores::Otros calificadores::/genética ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::recurrencia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::fracaso del tratamiento Genetic evolution and relapse-associated mutations in adult T-cell acute lymphoblastic leukemia patients treated in PETHEMA trials