Ribosomal proteins, miRNAs, and extracellular vesicles in myelodysplastic syndromes: molecular regulation and biomarker potential

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders caused by abnormalities at the hematopoietic stem cell level and are associated with ineffective hematopoiesis, peripheral cytopenias, and a propensity for leukemic transformation. Recent research elucidates the key mechanisms and roles of ribosomal proteins (RPs), microRNAs (miRNAs), extracellular vesicles (EVs), and long non-coding RNAs (lncRNAs) in the pathophysiology of MDS. Mutations or altered expression of RP genes lead to ribosomal stress and activation of p53, resulting in impaired erythropoiesis and apoptosis of hematopoietic progenitors. Dysregulation of miRNAs modulates gene expression programs that are essential for hematopoietic differentiation and apoptosis. Moreover, EV-associated miRNAs mediate multiple processes, including intercellular communication and regulation of the bone marrow (BM) microenvironment, thereby contributing to DNA damage and clonal evolution. EV-associated miR-10a and miR-15a have been reported to induce DNA damage in HSCs. LncRNAs have emerged as promising tools for cancer diagnosis and prognostic biomarkers. They play critical roles in regulating malignant cell proliferation, apoptosis, and epigenetic modifications. This overview highlights the molecular complexity of MDS pathogenesis, offering insights to support stratified diagnosis and the development of targeted therapies.