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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorGonzález Gil, Celia
dc.contributor.authorMorgades, Mireia
dc.contributor.authorLopes, Thaysa Fedalto
dc.contributor.authorFuster-Tormo, Francisco
dc.contributor.authorGarcía-Chica, Jesús
dc.contributor.authorZhao, Ran
dc.contributor.authorBarba Suñol, Pere
dc.date.accessioned2023-04-26T09:26:27Z
dc.date.available2023-04-26T09:26:27Z
dc.date.issued2023-04
dc.identifier.citationGonzález-Gil C, Morgades M, Lopes T, Fuster-Tormo F, García-Chica J, Zhao R, et al. Genomics improves risk stratifi cation of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials. Haematologica. 2023 Apr;108(4):969–80.
dc.identifier.issn1528-0020
dc.identifier.urihttps://hdl.handle.net/11351/9421
dc.descriptionGenomics; T-cell acute lymphoblastic leukemia
dc.description.abstractGenetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.
dc.language.isoeng
dc.publisherFerrata Storti Foundation
dc.relation.ispartofseriesHaematologica;108(4)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectGenòmica
dc.subjectLeucèmia limfoblàstica - Aspectes genètics
dc.subjectCèl·lules T
dc.subject.meshPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma
dc.subject.mesh/genetics
dc.subject.meshGenomics
dc.titleGenomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3324/haematol.2022.281196
dc.subject.decsleucemia-linfoma linfoblástico de células T precursoras
dc.subject.decs/genética
dc.subject.decsgenómica
dc.relation.publishversionhttps://doi.org/10.3324/haematol.2022.281196
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[González-Gil C, Lopes T, Fuster-Tormo F, García-Chica J] Institut d’Investigació contra la Leucemia Josep Carreras (IJC), Campus ICO-Germans Trias i Pujol, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Morgades M] Departament d’Hematologia Clínica, ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Zhao R] Department of Quantitative Health Sciences and Leukemia Program, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA. [Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid36325893
dc.identifier.wos000736413906053
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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