Etiopathogeny, prognosis and therapy of myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous and common group of clonal hematological disorders characterized by cytopenias, dysplastic changes of hematopoietic cells, and a high rate of transformation into acute myeloblastic leukemia (AML). MDS provide a clinical model for studying the emergency and progression of malignancy. The initiating events leading to MDS remain almost unknown. Imbalance of proliferative and differentiating capabilities of progenitor hematopoietic cells along with abnormalities in the normal process of apoptosis are involved in both the pathogenesis of MDS and transformation into AML. Multiple genomic lesions, comprising oncogene activation and tumor-suppressor gene inactivation, are probably required. Alkylating agents, cytotoxic drugs targeting topoisomerase II and benzene are the only clear etiological factors identified. Advanced age and great prognostic variability, not explained by the FAB subtype, complicates the design and analysis of clinical trials and therapy-planning. The use of recently developed prognostic scores for selecting the best treatment according to the expected risk is encouraged. In most patients therapy is unsatisfactory. At present, bone marrow transplantation is considered as the only curative approach. A better knowledge of the pathobiology of MDS should be valuable to develop new, more rationale and effective therapies.

A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies

“…Proposals for the pathogenesis of MDS have been suggested previously. [6][7][8][9] A specific multistep sequence for the development of adult-onset idiopathic MDS based on cell culture, cytokine, molecular and clinical research is presented (Figure 1). …”

Prevalence of Hemochromatosis Gene <i>(HFE)</i> Mutations in Greek Patients with Myelodysplastic Syndromes

“…MDS is a heterogeneous group of clonal hematopoietic disorders characterized by refractory cytopenias and a high rate of transformation to acute leukemia [2,3]. Owing to the refractory nature of their anemia, MDS patients need frequent blood transfusions entailing the accelerated development of secondary hemosiderosis [2,3]. Mutations in the HFE gene cause increased intestinal absorption, and 50-100% of patients with hereditary hemochromatosis (HH) are homozygous for the C282Y mutation [4][5][6].…”

“…MDS is a heterogeneous group of clonal hematopoietic disorders characterized by refractory cytopenias and a high rate of transformation to acute leukemia [2,3]. Owing to the refractory nature of their anemia, MDS patients need frequent blood transfusions entailing the accelerated development of secondary hemosiderosis [2,3].…”

Thalidomide therapy in adult patients with myelodysplastic syndrome

“…1,2 The specific pathogenesis of MDS is unknown. As many as 50% to 80% of MDS patients have cytogenetic abnormalities, which indicates that these disorders may represent a clonal evolution from a marrow stem cell with an acquired genetic mutation.…”