Abstract

Myelodysplastic Syndromes (MDS) represent a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and a risk of progression to acute myeloid leukemia (AML). Traditionally, MDS classification relied on morphological and cytogenetic assessments, but advancements in next-generation sequencing (NGS) have revealed recurrent genetic mutations that have reshaped the diagnostic and therapeutic landscape. This review article explores the clinical implications of molecular taxonomy in MDS, focusing on key mutations such as SF3B1, TP53, TET2, and ASXL1. The integration of molecular profiling into diagnostic frameworks, such as IPSS-Molecular (IPSS-M), has enhanced patient stratification and prognosis prediction. Moreover, targeted therapies, including Luspatercept for SF3B1-mutated MDS and hypomethylating agents for TET2 mutations, have emerged as promising treatments. However, challenges persist, including interpatient heterogeneity, clonal evolution, and limited access to molecular testing in clinical practice. This review article emphasizes the need for ongoing research and innovation to overcome these challenges, further integrating molecular insights into personalized MDS management to improve patient outcomes.