Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias. The natural history ranges from indolent forms lasting years to rapid evolution to acute myeloid leukemia (AML). MDS is classified by the French-American-British (FAB) system and World Health Organization (WHO) based on blast percentage and cytogenetic features. The International Prognostic Scoring System (IPSS) further stratifies patients by risk of progression or death. Known molecular abnormalities include mutations in genes such as TP53, RAS, and FMS.

1. Myelodysplastic syndromes Achievements in understanding and treatment

7. Known molecular abnormalities in MDS 5-10 Point mutation (codon 969 or rarely 301) FMS (encodes M-CSF receptor) 5 Point mutation or deletion of other allele P53 10-30% Point mutation (codon 12, 13 or 61) RAS (N or K) Incidence (%) Type of anomaly Gene

10. Myelodysplastic features in MDS Bone marrow: multinuclearity, nuclear fragments, megaloblastoid changes, cytoplasmic abnormalities, ringed sideroblasts Peripheral blood: Poikilocytosis, anisocytosis, nucleated red blood cells Dyserythropoiesis Bone marrow and/or peripheral blood findings MDS

11. Myelodysplastic features in MDS Micromegakariocytes Large mononucle a r forms Multiple small nuclei Dysmegakariopoiesis Nuclear abnormalities including: hypolobulation, ring-shaped nuclei, hypogranulation Dysgranulopoiesis Bone marrow and/or peripheral blood findings MDS