Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human CD43+ cells isolated from myelodysplastic syndrome patients and normal controls reveals involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.

ABSTRACT: 55 patients with MDS and 11 healthy controls were included in the study. At the time of investigation, 18 patients had RA, 19 RARS and 18 RAEB. The RAEB group was further subdivided into RAEB1 and RAEB2 for a selected part of the analysis. Bone marrow samples were obtained and CD34+ cells isolated from MDS patients and healthy controls using MACS magnetic cell separation columns. Total RNA was extracted using TRIZOL following the protocol supplied by the manufacturer. RNA was amplified using the Two-Cycle cDNA Synthesis and the Two-Cycle Target Labelling and Control Reagent packages (Affymetrix). Samples were hybridized to GeneChip Human Genome U133 Plus 2.0 arrays. Affymetrix CEL files were pre-processed using Robust MultiChip Analysis (RMA).

ORGANISM(S): Homo sapiens

DISEASE(S): normal

SUBMITTER: Andrea Pellagatti

PROVIDER: E-GEOD-4619 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.

Pellagatti Andrea A Cazzola Mario M Giagounidis Aristoteles A N AA Malcovati Luca L Porta Matteo G Della MG Killick Sally S Campbell Lisa J LJ Wang Li L Langford Cordelia F CF Fidler Carrie C Oscier David D Aul Carlo C Wainscoat James S JS Boultwood Jacqueline J

Blood 20060309 1

To gain insight into the poorly understood pathophysiology of the myelodysplastic syndromes (MDSs), we have determined the gene expression profiles of the CD34+ cells of 55 patients with MDS by using a comprehensive array platform. These profiles showed many similarities to reported interferon-gamma-induced gene expression in normal CD34+ cells; indeed the 2 most up-regulated genes, IFIT1 and IFITM1, are interferon-stimulated genes (ISGs). Alterations in the expression of ISGs may play a role in ...[more]

PMID: 16527891

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Project description:Inadequate extracellular conditions can adversely affect the environment of the ER and impinge on the maturation of nascent proteins. The resultant accumulation of unfolded proteins activates a signal transduction pathway, known as the unfolded protein response, which serves primarily to protect the cell during stress and helps restore homeostasis to the ER. Microarray analysis of the unfolded protein response in a human medulloblastoma cell line treated with thapsigargin revealed that, in addition to known targets, a large number of proangiogenic factors were up-regulated. Real-time PCR analyses confirmed that four of these factors, VEGF, FGF2, angiogenin and IL-8, were transcriptionally up-regulated in multiple cell lines by various ER stress inducers. Our studies on VEGF regulation revealed that XBP-1(S), a UPR-inducible transcription factor, bound to two regions on the VEGF promoter, and analysis of XBP-1 null mouse embryonic fibroblasts revealed that it contributes to VEGF expression in response to ER stress. ATF4, another UPR-inducible transcription factor, also binds to the VEGF gene, although its contribution to VEGF transcription appeared to be fairly modest. We also found that VEGF mRNA stability is increased in response to UPR activation, via activation of the AMP and p38MAP kinases, demonstrating that increased mRNA levels occur at two regulatory points. In keeping with the mRNA levels, we found that VEGF protein is secreted at levels as high as or higher than that achieved in response to hypoxia. Our results indicate that the UPR plays a significant role in inducing positive regulators of angiogenesis. It also regulates VEGF expression at multiple levels and is likely to have widespread implications for promoting angiogenesis in response to normal physiological cues as well as in pathological conditions like cancer. We used microarrays to perform genome wide expression analysis in Daoy medulloblastoma cells to identify gene profiles that change in response to thapsigargin treatment which causes induction of the unfolded protein response.

Dataset Information

Transcription profiling of human CD43+ cells isolated from myelodysplastic syndrome patients and normal controls reveals involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.

Publications

Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.

Similar Datasets

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