2026-06-14T10:38:52Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/164862024-11-28T15:59:29Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19608col_20.500.12105_16938col_20.500.12105_16977
Repisalud
author
Villa-Morales, María
author
Pérez-Gómez, Laura
author
Pérez-Gómez, Eduardo
author
López-Nieva, Pilar
author
Fernandez-Navarro, Pablo L
author
Santos, Javier
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación Ramón Areces
funder
Banco Santander
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Centro de Biología Molecular Severo Ochoa
2023-09-25T10:53:55Z
2023-09-25T10:53:55Z
2023-06-19
Int J Mol Sci. 2023 Jun 19;24(12):10350.
10.3390/ijms241210350
1422-0067
International journal of molecular sciences
37373496
http://hdl.handle.net/20.500.12105/16486
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.
eng
T-cell acute lymphoblastic leukaemia (T-ALL)
NRF2 (nuclear factor erythroid 2-related factor 2)
Prognostic biomarker
Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia
research article
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IdentificationNRF2ActivationPrognostic_2023.pdf
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Supplementary IdentificationNRF2ActivationPrognostic_2023.pdf
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IdentificationNRF2ActivationPrognostic_2023.pdf.txt
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Supplementary IdentificationNRF2ActivationPrognostic_2023.pdf.txt