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Title: | Genomics improves risk stratifi cation of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials |
Author: | González Gil, Celia Morgades, Mireia Lopes, Thaysa Fuster Tormo, Francisco García Chica, Jesús Zhao, Ran Montesinos, Pau Torrent, Anna Diaz Beya, Marina Coll, Rosa Hermosín, Lourdes Mercadal, Santiago González Campos, José Zamora, Lurdes Artola, Teresa Vall Llovera, Ferran Tormo, Mar Gil Cortés, Cristina Barba, Pere Novo, Andrés Ribera, Jordi Bernal, Teresa López de Ugarriza, Paula Queipo de Llano, María Paz Martínez Sánchez, Pilar Giménez, Alicia González Martínez, Teresa Cladera, Antonia Cervera, José Fernández Martín, Rosa Ardaiz, María Ángeles Vidal, María Jesús Baena, Ángela López Bigas, Nuria Bigas Salvans, Anna Maciejewski, Jaroslaw Orfao, Alberto Ribera, Josep Maria Genescà, Eulàlia |
Keywords: | Limfomes Cèl·lules T Lymphomas T cells |
Issue Date: | 3-Nov-2022 |
Publisher: | Ferrata Storti Foundation (Haematologica) |
Abstract: | Genetic 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 clinical -biological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Espanol de Tratamientos en Hematologia) 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3324/haematol.2022.281196 |
It is part of: | Haematologica, 2022, vol. 108, num. 4, p. 969-980 |
URI: | http://hdl.handle.net/2445/199865 |
Related resource: | https://doi.org/10.3324/haematol.2022.281196 |
ISSN: | 1592-8721 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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