Abstract
Myelodysplastic neoplasms represent a diverse group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an inherent risk of progression to acute myeloid leukemia. Accurate risk assessment and patient stratification are critical to optimizing therapeutic approaches and clinical outcomes. In 2022, significant advancements reshaped both the classification and prognostic stratification of MDSs. The revised WHO Classification introduced crucial genetically defined subtypes, particularly those involving biallelic TP53 inactivation and SF3B1 mutations, shifting the emphasis from traditional morphology-based criteria to molecular ones. Simultaneously, morphological subtypes such as hypoplastic and hyperfibrotic MDSs were established as distinct entities with unique prognostic implications. At the same time, the introduction of the International Molecular Prognostic Scoring System (IPSS-M) provided a more precise prognostic stratification by integrating comprehensive molecular data alongside traditional clinical and cytogenetic parameters. Several validation studies have confirmed IPSS-M's superior discriminative power compared to previous models, notably IPSS-R, improving predictions regarding overall survival and leukemia transformation. Nevertheless, practical considerations regarding the widespread application of IPSS-M have emerged, including concerns over economic feasibility and accessibility of advanced molecular testing methods, such as extensive Next-Generation Sequencing panels. This review synthesizes the recent literature and critical studies validating these classification and prognostic updates, discussing their clinical impact, practical considerations, and implications for targeted therapeutic strategies. By focusing on molecular pathogenesis, the latest classification systems and prognostic models promise significant advances in patient-specific management, setting the stage for future innovations in treatment and improved patient outcomes.