Abstract
The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified.
Highlights
Myelodysplastic syndromes (MDS) are clonal hematological disorders characterized by blood cytopenias, ineffective hematopoiesis and hypercellular bone marrow [1]
Our study has shown that SLC25A37 and SLC25A38 were over-expressed in refractory anemia with ring sideroblasts (RARS) patients, and has identified one sequence change in the ALAD gene that could contribute to a better understanding of the pathogenesis of sideroblastic MDS
Genes associated with iron and mitochondrial metabolism represented the largest function group of genes involved: 38% (266 molecules) of the over-expressed genes were identified in this study
Summary
Myelodysplastic syndromes (MDS) are clonal hematological disorders characterized by blood cytopenias, ineffective hematopoiesis and hypercellular bone marrow [1]. According to the WHO classification (2008), six subtypes of MDS are distinguished: refractory cytopenia with unilineage dysplasia (RCUD), refractory anemia with ring sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia with excess blasts DNA Variants in Refractory Anemia with Ring Sideroblasts. MH is fully suported by an "Ayuda predoctoral de la Junta de Castilla y León" from "European Regional Development Fund". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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