title: Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts.
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.
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: del Rey
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Benito
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Fontanillo
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Campos-Laborie
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: Kamila
authors.initials: K
authors.lastname: Janusz
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC-Universidad de Salamanca, Salamanca, Spain.
authors.forename: Talía
authors.initials: T
authors.lastname: Velasco-Hernández
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Abáigar
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Hernández
authors.affiliation: Servicio de Hematología, Hospital Clínico de Valladolid, Valladolid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Cuello
authors.affiliation: Servicio de Hematología, Hospital Clínico de Valladolid, Valladolid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Borrego
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC-Universidad de Salamanca, Salamanca, Spain.
authors.forename: Dionisio
authors.initials: D
authors.lastname: Martín-Zanca
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: De Las Rivas
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Ken I
authors.initials: KI
authors.lastname: Mills
authors.affiliation: IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández-Rivas
mesh_terms: D000753:Anemia, Refractory / Q000235:genetics; D000756:Anemia, Sideroblastic / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010750:Phosphoproteins / Q000235:genetics; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics
chemical_list: D027682:Cation Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C561492:Slc25a37 protein, human; C553226:Slc25a38 protein, human; D007501:Iron