Rodríguez-García Alba, Morales María Luz, Garrido-García Vanesa, García-Baquero Irene, Leivas Alejandra, Carreño-Tarragona Gonzalo, Sánchez Ricardo, Arenas Alicia, Cedena Teresa, Ayala Rosa María, Bautista José M, Martínez-López Joaquín, Linares María
Department of Hematology, 16473 Hospital Universitario 12 de Octubre, Hematological Malignancies Clinical Research Unit H120-CNIO, 28041 Madrid, Spain.
Department of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain.
Antioxidants (Basel). 2019 Oct 24;8(11):508. doi: 10.3390/antiox8110508.
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.
控制骨髓（BM）中的氧化应激是维持造血细胞自我更新、增殖和分化之间相互作用的关键。这种调节的破坏可导致以骨髓衰竭为特征的疾病，如骨髓增生异常综合征（MDS）。为了更好地理解氧化应激在MDS发展中的作用，我们比较了蛋白质羰基化作为MDS患者和对照受试者骨髓中氧化应激的指标，以及接受铁螯合剂地拉罗司（DFX）治疗的MDS患者。正如预期的那样，在MDS患者和对照的骨髓样本中观察到蛋白质羰基化模式的差异，前者的蛋白质羰基化增加。引人注目的是，与未治疗的患者相比，接受DFX治疗的患者骨髓中蛋白质羰基化水平较低。蛋白质组学分析确定了MDS骨髓细胞中四种羰基化水平高的蛋白质。最后，由于氧化应激相关信号通路可通过p53调节细胞周期，我们分析了骨髓细胞中p53靶基因p21的表达，发现其在MDS患者中显著上调，在DFX治疗后显著下调。总体而言，我们的结果表明，调节MDS患者骨髓中的氧化应激水平可能控制恶性进展。
