Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer.
Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer.
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DOI：
10.1186/1471-2164-10-442
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发表时间：
2009-09-18
期刊：
影响因子：
4.4
通讯作者：
Dianzani I
中科院分区：
文献类型：
--
作者：
Avondo F;Roncaglia P;Crescenzio N;Krmac H;Garelli E;Armiraglio M;Castagnoli C;Campagnoli MF;Ramenghi U;Gustincich S;Santoro C;Dianzani I
Diamond-Blackfan贫血（DBA）是一种罕见的遗传性红细胞发育不全，其特征是红系祖细胞成熟缺陷，在某些情况下与畸形有关。患者患实体瘤的风险增加。在核糖体蛋白（RP）基因RPS 19、RPS 24、RPS 17、RPL 5、RPL 11、RPL 35 A中发现了突变。对患者造血祖细胞的研究表明，RP的单倍不足会损害rRNA加工和核糖体生物合成。DBA淋巴细胞显示蛋白质合成减少，成纤维细胞显示异常rRNA加工和增殖受损。为了评估DBA中非造血组织的参与，我们分析了DBA患者与健康对照组成纤维细胞中的全局基因表达。微阵列表达谱分析使用AffysseGeneChip人类基因组U133 A 2.0阵列揭示了421个基因在DBA患者成纤维细胞中差异表达。这些基因包括一大簇核糖体蛋白和参与蛋白质合成和氨基酸代谢的因子，以及与细胞死亡、癌症和组织发育相关的基因。该分析首次报告了DBA中非造血细胞类型的异常基因表达谱。这些数据支持DBA可能是由于一般或特定蛋白质合成缺陷的假设。
Diamond-Blackfan anaemia (DBA) is a rare inherited red cell hypoplasia characterised by a defect in the maturation of erythroid progenitors and in some cases associated with malformations. Patients have an increased risk of solid tumors. Mutations have been found in several ribosomal protein (RP) genes, i.e RPS19, RPS24, RPS17, RPL5, RPL11, RPL35A. Studies in haematopoietic progenitors from patients show that haplo-insufficiency of an RP impairs rRNA processing and ribosome biogenesis. DBA lymphocytes show reduced protein synthesis and fibroblasts display abnormal rRNA processing and impaired proliferation. To evaluate the involvement of non-haematopoietic tissues in DBA, we have analysed global gene expression in fibroblasts from DBA patients compared to healthy controls. Microarray expression profiling using Affymetrix GeneChip Human Genome U133A 2.0 Arrays revealed that 421 genes are differentially expressed in DBA patient fibroblasts. These genes include a large cluster of ribosomal proteins and factors involved in protein synthesis and amino acid metabolism, as well as genes associated to cell death, cancer and tissue development. This analysis reports for the first time an abnormal gene expression profile in a non-haematopoietic cell type in DBA. These data support the hypothesis that DBA may be due to a defect in general or specific protein synthesis.
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影响因子：
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