Myelodysplastic syndrome (MDS) is a heterogenous group of clonal hematopoietic disorders. Chromosomal abnormalities detected in this disease were the start to many studies in order to characterize molecular pathogenesis. The loss of genetic material observed in most patients with MDS leads to the hypothesis of tumor suppressor genes (TSG), but this theory does not explain the initial event that underlies growth advantage of hematopoietic progenitor cells, though, different mechanisms are involved such as oncogene activation, altered signaling components and transcription factors. Oncogene mutations, such as RAS, P53, PDGF, FLT3 and MLL, for instance, may contribute to the development of MDS. Tandem mutation of FLT3 is a genetic event that occurs late in the course of the disease and these patients tend to present unfavorable prognosis and imminent transformation into acute myeloid leukemia. Quantitative as well as qualitative abnormalities of transcription factors are detected in MDS and induce the unbalance or block in the differentiation of hematopoietic cells, that results in ineffective hematopoiesis. Epigenentic alterations are characterized by DNA methylation that exerts a role in controlling genic expression. Hypermethylation and inactivation of regulating genes act in the development of the disease. There is a high risk of MDS when p15INK4B is inactivated due to hypermethylation of its promoter. Telomere shortening correlates with complex karyotypes indicating genomic instability and poor prognosis.
Chromosome; myelodysplasic syndrome; FISH; PCR; prognosis; FLT3; LOH