Recent advances in defining low- and intermediate-risk myelodysplastic syndromes (MDSs) have emphasized the critical role of molecular characterization using next-generation sequencing (NGS). Molecular profiling significantly enhances diagnostic precision, classification, and risk stratification, thereby informing therapeutic decisions, including the timing of hematopoietic stem-cell transplantation (HSCT). The Molecular International Prognostic Scoring System integrates clinical and molecular data, reclassifying and upstaging a substantial number of patients compared with previous prognostic systems, possibly allowing for more tailored therapeutic interventions. The novel therapeutic agents luspatercept and imetelstat have been particularly impactful. Luspatercept, which is effective in lower-risk (LR)-MDS, especially but not only in SF3B1-mutated cases, promotes late-stage erythroid maturation and transfusion independence (TI). Imetelstat, a telomerase inhibitor, induces TI while demonstrating disease-modifying effects as it significantly reduces mutation allele frequencies in patients who respond. These agents exemplify personalized medicine, emphasizing treatment selection and timing based on individual molecular and clinical features. Current research focuses on optimizing therapeutic strategies and exploring combination treatments to improve clinical outcomes.
