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Article

Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia

by
María Villa-Morales
1,2,3,4,*,
Laura Pérez-Gómez
1,2,
Eduardo Pérez-Gómez
5,6,
Pilar López-Nieva
1,2,3,4,
Pablo Fernández-Navarro
7,8 and
Javier Santos
1,2,3,4,*
1
Department of Biology, Universidad Autónoma de Madrid, 28049 Madrid, Spain
2
Department of Genome Dynamics and Function, Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain
3
Area of Genetics and Genomics, IIS Fundación Jiménez Díaz, 28040 Madrid, Spain
4
Institute for Molecular Biology-IUBM, Universidad Autónoma de Madrid, 28049 Madrid, Spain
5
Departamento de Bioquímica y Biología Molecular, Universidad Complutense de Madrid, 28040 Madrid, Spain
6
Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain
7
Unit of Cancer and Environmental Epidemiology, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, 28029 Madrid, Spain
8
Networking Biomedical Research Centre of Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(12), 10350; https://doi.org/10.3390/ijms241210350
Submission received: 19 May 2023 / Revised: 15 June 2023 / Accepted: 16 June 2023 / Published: 19 June 2023
(This article belongs to the Special Issue Insights in New Biomarkers and Molecular Drug Targets in Hematological Neoplasias)
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Abstract

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.
Keywords: T-cell acute lymphoblastic leukaemia (T-ALL); NRF2 (nuclear factor erythroid 2-related factor 2); prognostic biomarker T-cell acute lymphoblastic leukaemia (T-ALL); NRF2 (nuclear factor erythroid 2-related factor 2); prognostic biomarker

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MDPI and ACS Style

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

AMA Style

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. International Journal of Molecular Sciences. 2023; 24(12):10350. https://doi.org/10.3390/ijms241210350

Chicago/Turabian Style

Villa-Morales, María, Laura Pérez-Gómez, Eduardo Pérez-Gómez, Pilar López-Nieva, Pablo Fernández-Navarro, and Javier Santos. 2023. "Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia" International Journal of Molecular Sciences 24, no. 12: 10350. https://doi.org/10.3390/ijms241210350

APA Style

Villa-Morales, M., Pérez-Gómez, L., Pérez-Gómez, E., López-Nieva, P., Fernández-Navarro, P., & Santos, J. (2023). Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia. International Journal of Molecular Sciences, 24(12), 10350. https://doi.org/10.3390/ijms241210350

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