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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia, Refractory / genetics
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Anemia, Sideroblastic / genetics*
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Anemia, Sideroblastic / metabolism
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Cation Transport Proteins / genetics
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DNA Mutational Analysis / methods*
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Gene Expression Profiling / methods
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Gene Expression Regulation*
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Genetic Predisposition to Disease
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Humans
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Iron / metabolism*
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Mitochondria / genetics
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Mitochondria / metabolism*
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Proteins / genetics
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Oligonucleotide Array Sequence Analysis / methods
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Phosphoproteins / genetics
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RNA Splicing Factors
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Ribonucleoprotein, U2 Small Nuclear / genetics
Substances
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Cation Transport Proteins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Proteins
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Phosphoproteins
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RNA Splicing Factors
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Ribonucleoprotein, U2 Small Nuclear
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SF3B1 protein, human
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Slc25a37 protein, human
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Slc25a38 protein, human
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Iron
Grants and funding
This work was partially supported by grants from: the Spanish Fondo de Investigaciones Sanitarias (PI14/1971, PI12/00281); Proyectos de Investigación del SACYL (BIO/SA52/14, BIO/SA10/14, BIO/SA31/13, GRS 994/A/14); Consejería Educación, Junta Castilla y León (HUS272U13); COST Action "EuGESMA" (BM0801); Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) "Una manera de hacer Europa" (Innocampus) (RD12/0036/0069, RD12/0036/0029, RD12/0036/0044); European Union's Seventh Framework Programme (FP7/2007-2013 nº 306242- NGS-PTL). MDR is fully supported by a "Grant from Fundación Española de Hematología y Hemoterapia". MA was fully supported by a "Grant from the Spanish Consejo Superior de Investigaciones Científicas, Junta para la Ampliación de Estudios (JAE Predoctoral) [09-02402]". MH is fully suported by an "Ayuda predoctoral de la Junta de Castilla y León" from "European Regional Development Fund". DMZ was funded by the Spanish Ministry of Science and Innovation (PI082025) and Junta de Castilla y León (CSI224A11-2, SAN/103/2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.