del Rey Mónica, Benito Rocío, Fontanillo Celia, Campos-Laborie Francisco J, Janusz Kamila, Velasco-Hernández Talía, Abáigar María, Hernández María, Cuello Rebeca, Borrego Daniel, Martín-Zanca Dionisio, De Las Rivas Javier, Mills Ken I, Hernández-Rivas Jesús M
IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.
Instituto de Biología Funcional y Genómica, CSIC-Universidad de Salamanca, Salamanca, Spain.
PLoS One. 2015 May 8;10(5):e0126555. doi: 10.1371/journal.pone.0126555. eCollection 2015.
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.
SF3B1基因突变的存在是环形铁粒幼细胞难治性贫血（RARS）的一个标志。然而，导致环形铁粒幼细胞骨髓增生异常综合征（MDS-RS）特征性铁蓄积的机制尚未完全明确。为了深入了解MDS-RS的分子基础，我们对与铁和线粒体代谢相关基因的表达及突变状态进行了综合研究。共研究了231例低危MDS患者和81例对照。基因表达分析显示，与对照及单系发育异常难治性血细胞减少症（RCUD）相比，RARS患者中与铁代谢和线粒体功能相关的失调基因数量最多。因此，线粒体转运蛋白SLC25（SLC25A37和SLC25A38）和ALAD基因在RARS中过表达。此外，在有SF3B1突变的患者和无突变的患者之间观察到显著差异。铁和线粒体代谢相关基因的失调为我们对MDS-RS的认识提供了新的见解。已鉴定出可能参与这些疾病发病机制的新变异。
