REVIEW ARTICLE The Myelodysplastic Syndromes: Biology and Implications for Management

Since the initial efforts to characterize the myelodys-plastic syndromes in 1976, an extensive body of information has accumulated defining biologic fea-tures and the relation to clinical aspects of disease. While the pathogenesis of these disorders remains incompletely understood, laboratory investigations in-dicate that they are clonal disorders affecting he-matopoietic stem cells characterized by a progressive imbalance between self-renewal and differentiation. Despite karyotypic resemblance to acute myeloid leu-kemia, fundamental biologic differences may underly the disappointing results achieved to date with inten-M ORE THAN a decade has passed since the French-American-British (FAB) Co-operative Group first characterized the myelo-dysplastic syndromes and proposed diagnostic criteria for their recognition. ' In 1982, the classi-fication was expanded to include five disorders distinguishable by morphologic features: refrac-tory anemia (RA), refractory anemia with ringed sideroblasts (RARS), chronic myelomonocytic leukemia (CMML), refractory anemia with ex-cess blasts (RAEB), and RAEB-in-transforma-tion (RAEB-T).2 These disorders by definition share histologic features of hematopoietic dyspla-sia and display a varied propensity for leukemic transformation. The natural history of the myelodysplastic syndromes varies widely, ranging from chronic anemias with low propensity for leukemic conver-sion to disorders characterized by profound dis-turbance in blood-cell production with a high ris