Oxidative Stress and Its Role in the Emergence and Progression of Myelodysplastic Syndromes: Insights from Proteomic...

Myelodysplastic syndromes (MDS) belong to a category of malignant stem-cell and myeloid disorders that deteriorate the function of the hematopoietic system exacerbated by the omnipresent anemia that characterizes myelodysplasia. The pathogenesis of MDS is driven by cytogenetic abnormalities along with the excessive production of pro-inflammatory cytokines and disruptions in inflammatory signaling pathway, particularly through the influence of carbonylated proteins, which are linked to MDS progression. An additional and major contributor to the pathogenesis of MDS is oxidative stress marked by uncontrolled levels of reactive oxygen species (ROS), which have been suggested as potential biomarkers for assessing disease severity and stratifying MDS cases throughout a variety of methods. Excessive and non-accumulative levels of free iron can also lead to iron overload (IOL)-related promotion of a high oxidative state, whether we refer to treatment-related IOL or natural IOL mechanisms. Proteomic analysis has emerged as a powerful tool for profiling protein samples, and, consequently, understanding the molecular changes underlying MDS. In this review, we evaluated studies and their methodologies aiming in investigating distinctive proteomics signatures associated with MDS pathogenesis, focusing on the role of oxidative stress at the protein level.