The myelodysplastic syndromes: biology and implications for management

Since the initial efforts to characterize the myelodysplastic syndromes in 1976, an extensive body of information has accumulated defining biologic features and the relation to clinical aspects of disease. While the pathogenesis of these disorders remains incompletely understood, laboratory investigations indicate that they are clonal disorders affecting hematopoietic stem cells characterized by a progressive imbalance between self-renewal and differentiation. Despite karyotypic resemblance to acute myeloid leukemia, fundamental biologic differences may underly the disappointing results achieved to date with intensive chemotherapy. The recent availability of recombinant hematopoietic growth factors for use in clinical trials has shown that the maturation defect in many instances can be overcome with administration of lineage-restricted recombinant hematopoietins. Routine use of these promising agents must await results of randomized clinical trials to determine the impact of prolonged treatment on leukemic evolution and disease-related morbidity.