Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16486
Título
Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia
Autor(es)
Fecha de publicación
2023-06-19
Cita
Int J Mol Sci. 2023 Jun 19;24(12):10350.
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
T-cell acute lymphoblastic leukaemia (T-ALL) | NRF2 (nuclear factor erythroid 2-related factor 2) | Prognostic biomarker
MESH
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | Humans | NF-E2-Related Factor 2 | Prognosis | Phosphatidylinositol 3-Kinases | Neoplasm Recurrence, Local | T-Lymphocytes
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- IdentificationNRF2ActivationPr ...
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- Supplementary IdentificationNR ...
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- 1.539Mb
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