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Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer

BACKGROUND: 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 pro...

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Autores principales: Avondo, Federica, Roncaglia, Paola, Crescenzio, Nicoletta, Krmac, Helena, Garelli, Emanuela, Armiraglio, Marta, Castagnoli, Carlotta, Campagnoli, Maria Francesca, Ramenghi, Ugo, Gustincich, Stefano, Santoro, Claudio, Dianzani, Irma
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760583/
https://www.ncbi.nlm.nih.gov/pubmed/19765279
http://dx.doi.org/10.1186/1471-2164-10-442
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author Avondo, Federica
Roncaglia, Paola
Crescenzio, Nicoletta
Krmac, Helena
Garelli, Emanuela
Armiraglio, Marta
Castagnoli, Carlotta
Campagnoli, Maria Francesca
Ramenghi, Ugo
Gustincich, Stefano
Santoro, Claudio
Dianzani, Irma
author_facet Avondo, Federica
Roncaglia, Paola
Crescenzio, Nicoletta
Krmac, Helena
Garelli, Emanuela
Armiraglio, Marta
Castagnoli, Carlotta
Campagnoli, Maria Francesca
Ramenghi, Ugo
Gustincich, Stefano
Santoro, Claudio
Dianzani, Irma
author_sort Avondo, Federica
collection PubMed
description BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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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spelling pubmed-27605832009-10-13 Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer Avondo, Federica Roncaglia, Paola Crescenzio, Nicoletta Krmac, Helena Garelli, Emanuela Armiraglio, Marta Castagnoli, Carlotta Campagnoli, Maria Francesca Ramenghi, Ugo Gustincich, Stefano Santoro, Claudio Dianzani, Irma BMC Genomics Research Article BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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. BioMed Central 2009-09-18 /pmc/articles/PMC2760583/ /pubmed/19765279 http://dx.doi.org/10.1186/1471-2164-10-442 Text en Copyright © 2009 Avondo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Avondo, Federica
Roncaglia, Paola
Crescenzio, Nicoletta
Krmac, Helena
Garelli, Emanuela
Armiraglio, Marta
Castagnoli, Carlotta
Campagnoli, Maria Francesca
Ramenghi, Ugo
Gustincich, Stefano
Santoro, Claudio
Dianzani, Irma
Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
title Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
title_full Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
title_fullStr Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
title_full_unstemmed Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
title_short Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
title_sort fibroblasts from patients with diamond-blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760583/
https://www.ncbi.nlm.nih.gov/pubmed/19765279
http://dx.doi.org/10.1186/1471-2164-10-442
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