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Antioxidants (Basel). 2019 Oct 24;8(11). pii: E508. doi: 10.3390/antiox8110508.

Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy.

Author information

1
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. albarodriguezgarcia@hotmail.com.
2
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. mlmorales17@gmail.com.
3
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. gvaneg@hotmail.com.
4
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. irene.g.baquero@gmail.com.
5
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. alejandraleial@gmail.com.
6
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. gonzalocarreno.gomeztarragona@gmail.com.
7
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. ricardsanchez.hdoc@gmail.com.
8
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. arenasalic@gmail.com.
9
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. mariateresa.cedena@salud.madrid.org.
10
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. rayaladiaz12@gmail.com.
11
Department of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain. jmbau@vet.ucm.es.
12
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. jmarti01@med.ucm.es.
13
Department of Medicine, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain. jmarti01@med.ucm.es.
14
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain. mlinares@ucm.es.
15
Department of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain. mlinares@ucm.es.

Abstract

Control of oxidative stress in the bone marrow (BM) is key for maintaining the interplay between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an indicator of oxidative stress in the BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox (DFX). As expected, differences in the pattern of protein carbonylation were observed in BM samples between MDS patients and controls, with an increase in protein carbonylation in the former. Strikingly, patients under DFX treatment had lower levels of protein carbonylation in BM with respect to untreated patients. Proteomic analysis identified four proteins with high carbonylation levels in MDS BM cells. Finally, as oxidative stress-related signaling pathways can modulate the cell cycle through p53, we analyzed the expression of the p53 target gene p21 in BM cells, finding that it was significantly upregulated in patients with MDS and was significantly downregulated after DFX treatment. Overall, our results suggest that the fine-tuning of oxidative stress levels in the BM of patients with MDS might control malignant progression.

KEYWORDS:

carbonylation; deferasirox; myelodysplastic syndromes; oxidative stress

PMID:
31652983
DOI:
10.3390/antiox8110508
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