RT Journal Article T1 Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia A1 Villa-Morales, María A1 Pérez-Gómez, Laura A1 Pérez Gómez, Eduardo A1 López-Nieva, Pilar A1 Fernández-Navarro, Pablo A1 Santos, Javier AB 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. PB MDPI SN 1422-0067 YR 2023 FD 2023-06-19 LK https://hdl.handle.net/20.500.14352/104813 UL https://hdl.handle.net/20.500.14352/104813 LA eng NO Villa-Morales, M.; Pérez-Gómez, L.; Pérez-Gómez, E.; López-Nieva, P.; Fernández-Navarro, P.; Santos, J. Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia. Int. J. Mol. Sci. 2023, 24, 10350. https://doi.org/10.3390/ijms241210350 DS Docta Complutense RD 4 abr 2025