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



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Rodríguez-García, Alba and Morales, María Luz and Garrido-García, Vanesa and García-Baquero, Irene and Leivas, Alejandra and Carreño-Tarragona, Gonzalo and Sánchez, Ricardo and Arenas, Alicia and Cedena, Teresa and Ayala, Rosa María and Bautista Santa Cruz, José Manuel and Martínez López, Joaquín and Linares Gómez, María (2019) Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy. Antioxidants, 8 (11). p. 508. ISSN 2076-3921

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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.

Item Type:Article
Uncontrolled Keywords:myelodysplastic syndromes; carbonylation; oxidative stress; deferasirox
Subjects:Medical sciences > Medicine > Medical microbiology
ID Code:65734
Deposited On:27 May 2021 13:48
Last Modified:28 May 2021 07:35

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