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Title: Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients
Authors: Gonçalves, Ana Cristina 
Alves, Raquel 
Baldeiras, Inês 
Jorge, Joana 
Marques, Bárbara 
Paiva, Artur 
Oliveiros, Bárbara 
Cortesão, Emília 
Costa, José Manuel Nascimento 
Sarmento-Ribeiro, Ana Bela 
Keywords: myelodysplastic syndrome; erythropoiesis-stimulating agents; response biomarker; oxidative stress; antioxidant defenses; reactive oxygen species
Issue Date: 2021
Publisher: Frontiers Media S.A.
Project: UID/NEU/04539/2019 
POCI-01-0145- FEDER-007440 
Serial title, monograph or event: Frontiers in Cell and Developmental Biology
Volume: 9
Abstract: Oxidative stress has been implicated in the development of several types of cancer, including myelodysplastic syndromes (MDS), as well as in the resistance to treatment. In this work, we assessed the potential of oxidative stress parameters to predict the response to erythropoiesis-stimulating agents (ESAs) in lower-risk MDS patients. To this end, we analyzed the systemic levels of reactive species (peroxides and NO), antioxidant defenses (uric acid, vitamin E, vitamin A, GSH, GSSG, TAS, as well as GPX and GR activities], and oxidative damage (8-OH-dG and MDA) in 66 MDS patients, from those 44 have been treated with ESA. We also calculated the peroxides/TAS and NO/TAS ratios and analyzed the gene expression of levels of the redox regulators, NFE2L2 and KEAP1. We found that patients that respond to ESA treatment showed lower levels of plasma peroxides (p < 0.001), cellular GSH (p < 0.001), and cellular GR activity (p = 0.001) when compared to patients who did not respond to ESA treatment. ESA responders also showed lower levels of peroxides/TAS ratio (p < 0.001) and higher levels of the expression of the NFE2L2 gene (p = 0.001) than those that did not respond to ESA treatment. The levels of plasmatic peroxides shown to be the most accurate biomarker of ESA response, with good sensitivity (80%) and specificity (100%) and is an independent biomarker associated with therapy response. Overall, the present study demonstrated a correlation between oxidative stress levels and the response to ESA treatment in lower-risk MDS patients, with the plasmatic peroxides levels a good predictive biomarker of drug (ESA) response.
ISSN: 2296-634X
DOI: 10.3389/fcell.2021.701328
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais

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