Beyond Morphology: Molecular Drivers, Updated Classifications, and Novel Therapeutics in Myelodysplastic Syndromes

Abstract

Background: Myelodysplastic syndromes/neoplasms (MDS) are clonal myeloid disorders characterized by ineffective hematopoiesis, cytopenias, and a variable risk of progression to acute myeloid leukemia (AML). Morphology remains central to diagnosis, but cytogenetic and molecular findings increasingly inform disease classification, prognosis, and treatment selection. Review Approach: This narrative review draws on a selective PubMed literature search covering 2008–2022 and on relevant classification and prognostic publications. Conclusion: MDS assessment requires integration of blood counts, peripheral-blood and bone-marrow morphology, cytogenetics, and molecular findings. The WHO fifth edition and the International Consensus Classification (ICC), both published in 2022, place greater emphasis on genetically defined entities, while prognostic tools such as IPSS-R and IPSS-M support risk assessment. Treatment remains dependent on disease risk, cytopenias, molecular features, patient fitness, and transplant eligibility.

Keywords: Myelodysplastic syndromes; Molecular pathogenesis; WHO fifth edition; International Consensus Classification; Next-generation sequencing; IPSS-M; Risk stratification; Targeted therapy; Acute myeloid leukemia; Hematopoietic stem cell transplantation.