Polymorphisms in Tgf[Beta] and Tnf[Alpha] are Associated with the Myelodysplastic Syndrome Phenotype (Transforming Growth Factor) (Tumor Necrosis Factor) (Report‪)‬

The myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, multilineage dysplasia, peripheral cytopenias, and susceptibility to leukemia. (1) Demonstrating a varied spectrum of biologic, genetic, morphologic, and clinical characteristics, MDS has a natural history ranging from enduring years of indolent disease to an accelerated progression toward acute leukemia. The diagnosis of MDS, particularly the low-grade varieties such as refractory anemia, is difficult in the absence of supportive findings (ie, clonal cytogenetic abnormalities), and early stages may be underdiagnosed. The only known curative treatment available is bone marrow transplantation. Only with a full characterization of the pathobiology of MDS will better and targeted therapies be developed and earlier diagnosis possible. The etiology and pathophysiology of myelodysplasia is poorly understood. Mechanisms of disease include pluripotent stem cell damage and abnormalities in proliferation, differentiation, maturation, and apoptosis leading to an ineffective hematopoiesis. (1) Like most malignancies, (2) MDS is presumed to develop from multiple genetic aberrations generating the developmental phenotypes seen in the hematopoietic lineage. Except for a polymorphism in the granulocyte colony-stimulating factor receptor that is associated with high-risk MDS, (3) the genetic risk factors that predispose to the development of MDS are unknown.