ETIOPATHOLOGY, PROGNOSIS AND THERAPY OF MYELODYSPLASTIC SYNDROMES

Myelodysplastic syndromes (MDS) are a heterogeneous and common group o f clonal hematological disorders characterized by cytopenias, dysplast ic changes of hematopoietic cells, and a high rate of transformation i nto acute myeloblastic leukemia (AML). MDS provide a clinical model fo r studying the emergency and progression of malignancy. The initiating events leading to MDS remain almost unknown. Imbalance of proliferati ve and differentiating capabilities of progenitor hematopoietic cells along with abnormalities in the normal process of apoptosis are involv ed in both the pathogenesis of MDS and transformation into AML. Multip le genomic lesions, comprising oncogene activation and tumor-suppresso r gene inactivation, are probably required. Alkylating agents, cytotox ic drugs targeting topoisomerase II and benzene are the only clear eti ological factors identified. Advanced age and great prognostic variabi lity, not explained by the FAB subtype, complicates the design and ana lysis of clinical trials and therapy-planning. The use of recently dev eloped prognostic scores for selecting the best treatment according to the expected risk is encouraged. In most patients therapy is unsatisf actory. At present, bone marrow transplantation is considered as the o nly curative approach. A better knowledge of the pathobiology of MDS s hould be valuable to develop new, more rationale and effective therapi es.