TY - JOUR
T1 - Fibroblasts from patients with Diamond-Blackfan anaemia show abnormal expression of genes involved in protein synthesis, amino acid metabolism and cancer
AU - Avondo, Federica
AU - Roncaglia, Paola
AU - Crescenzio, Nicoletta
AU - Krmac, Helena
AU - Garelli, Emanuela
AU - Armiraglio, Marta
AU - Castagnoli, Carlotta
AU - Campagnoli, Maria F.
AU - Ramenghi, Ugo
AU - Gustincich, Stefano
AU - Santoro, Claudio
AU - Dianzani, Irma
N1 - Funding Information:
This work was funded from grants from the Diamond Blackfan Anemia Foundation (to I.D.), Telethon (to I.D.), PRIN 2006 (to I.D. and U.R.), Regione Piemonte Ricerca Sanitaria Finalizzata (to U.R.) and Compagnia San Paolo (to IRCAD). We thank Andrew Bradbury for the revision of the manuscript and helpful discussion. We also thank the Daniella Maria Arturi Foundation for supporting communication among DBA researchers.
PY - 2009/9/18
Y1 - 2009/9/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70350450581&partnerID=8YFLogxK
U2 - 10.1186/1471-2164-10-442
DO - 10.1186/1471-2164-10-442
M3 - Article
SN - 1471-2164
VL - 10
SP - 442
JO - BMC Genomics
JF - BMC Genomics
M1 - 1471
ER -
