Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia

The standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates of initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, with cure rates below 10% and limited therape...

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Detalles Bibliográficos
Autores: Villa Morales, María del Consuelo, Pérez-Gómez, Laura, Pérez-Gómez, Eduardo, López Nieva, María Pilar, Fernández -Navarro, Pablo, Santos Hernández, Francisco Javier
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/708548
Acceso en línea:http://hdl.handle.net/10486/708548
https://dx.doi.org/10.3390/ijms241210350
Access Level:acceso abierto
Palabra clave:Biological Marker
Glutathione
Mammalian Target of Rapamycin
Protein Kinase B
Transcription Factor Nrf2
Biología y Biomedicina / Biología
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spelling Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemiaVilla Morales, María del ConsueloPérez-Gómez, LauraPérez-Gómez, EduardoLópez Nieva, María PilarFernández -Navarro, PabloSantos Hernández, Francisco JavierBiological MarkerGlutathioneMammalian Target of RapamycinProtein Kinase BTranscription Factor Nrf2Biología y Biomedicina / BiologíaThe standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates of initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, with cure rates below 10% and limited therapeutic options. To ameliorate the clinical management of these patients, it is urgent to identify biomarkers able to predict their outcomes. In this work, we investigate whether NRF2 activation constitutes a biomarker with prognostic value in T-ALL. Using transcriptomic, genomic, and clinical data, we found that T-ALL patients with high NFE2L2 levels had shorter overall survival. Our results demonstrate that the PI3K-AKT-mTOR pathway is involved in the oncogenic signalling induced by NRF2 in T-ALL. Furthermore, T-ALL patients with high NFE2L2 levels displayed genetic programs of drug resistance that may be provided by NRF2-induced biosynthesis of glutathione. Altogether, our results indicate that high levels of NFE2L2 may be a predictive biomarker of poor treatment response in T-ALL patients, which would explain the poor prognosis associated with these patients. This enhanced understanding of NRF2 biology in T-ALL may allow a more refined stratification of patients and the proposal of targeted therapies, with the ultimate goal of improving the outcome of relapsed/refractory T-ALL patients.RTI2018-093330-B-I00MDPIDepartamento de Biología20232023-06-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/708548https://dx.doi.org/10.3390/ijms241210350reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7085482026-06-23T12:46:27Z
dc.title.none.fl_str_mv Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
title Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
spellingShingle Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
Villa Morales, María del Consuelo
Biological Marker
Glutathione
Mammalian Target of Rapamycin
Protein Kinase B
Transcription Factor Nrf2
Biología y Biomedicina / Biología
title_short Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
title_full Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
title_fullStr Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
title_full_unstemmed Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
title_sort Identification of NRF2 activation as a prognostic biomarker in T-cell acute lymphoblastic leukaemia
dc.creator.none.fl_str_mv Villa Morales, María del Consuelo
Pérez-Gómez, Laura
Pérez-Gómez, Eduardo
López Nieva, María Pilar
Fernández -Navarro, Pablo
Santos Hernández, Francisco Javier
author Villa Morales, María del Consuelo
author_facet Villa Morales, María del Consuelo
Pérez-Gómez, Laura
Pérez-Gómez, Eduardo
López Nieva, María Pilar
Fernández -Navarro, Pablo
Santos Hernández, Francisco Javier
author_role author
author2 Pérez-Gómez, Laura
Pérez-Gómez, Eduardo
López Nieva, María Pilar
Fernández -Navarro, Pablo
Santos Hernández, Francisco Javier
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología
dc.subject.none.fl_str_mv Biological Marker
Glutathione
Mammalian Target of Rapamycin
Protein Kinase B
Transcription Factor Nrf2
Biología y Biomedicina / Biología
topic Biological Marker
Glutathione
Mammalian Target of Rapamycin
Protein Kinase B
Transcription Factor Nrf2
Biología y Biomedicina / Biología
description The standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates of initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, with cure rates below 10% and limited therapeutic options. To ameliorate the clinical management of these patients, it is urgent to identify biomarkers able to predict their outcomes. In this work, we investigate whether NRF2 activation constitutes a biomarker with prognostic value in T-ALL. Using transcriptomic, genomic, and clinical data, we found that T-ALL patients with high NFE2L2 levels had shorter overall survival. Our results demonstrate that the PI3K-AKT-mTOR pathway is involved in the oncogenic signalling induced by NRF2 in T-ALL. Furthermore, T-ALL patients with high NFE2L2 levels displayed genetic programs of drug resistance that may be provided by NRF2-induced biosynthesis of glutathione. Altogether, our results indicate that high levels of NFE2L2 may be a predictive biomarker of poor treatment response in T-ALL patients, which would explain the poor prognosis associated with these patients. This enhanced understanding of NRF2 biology in T-ALL may allow a more refined stratification of patients and the proposal of targeted therapies, with the ultimate goal of improving the outcome of relapsed/refractory T-ALL patients.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-06-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/708548
https://dx.doi.org/10.3390/ijms241210350
url http://hdl.handle.net/10486/708548
https://dx.doi.org/10.3390/ijms241210350
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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