Bone marrow cell transcripts from Fanconi anaemia patients revealin vivoalterations in mitochondrial, redox and DNA repair pathways

Autor: Sandra Petrović, Luca Tiano, Giovanni Pagano, Beatriz Porto, Annarita Aiello Talamanca, Federico V. Pallardó, Giuseppe Castello, Marco d'Ischia, Adriana Zatterale
Přispěvatelé: Pagano, G, Talamanca, Aa, Castello, G, D'Ischia, Marco, Pallardo, Fv, Petrovic, S, Porto, B, Tiano, L, Zatterale, A.
Rok vydání: 2013
Předmět:
Male
DNA Repair
iron-chelating proteins
Transcriptome
0302 clinical medicine
Fanconi anemia
Gene expression
cytokine
oxidative stress
Child
bioenergetic pathway
Regulation of gene expression
0303 health sciences
Hematology
General Medicine
heat-shock protein
Mitochondria
3. Good health
030220 oncology & carcinogenesis
Female
Fanconi anaemia
Oxidation-Reduction
Signal Transduction
Adult
iron-chelating protein
DNA repair
Bone Marrow Cells
Biology
Proinflammatory cytokine
03 medical and health sciences
medicine
Humans
transcripts
Gene
030304 developmental biology
oxidative stre
Gene Expression Profiling
heat-shock proteins
Molecular Sequence Annotation
medicine.disease
Molecular biology
cytokines
DNA repair
Fanconi anaemia
bioenergetic pathways
cytokines
heat-shock proteins
iron-chelating proteins
oxidative stress
transcripts
Gene expression profiling
Oxidative Stress
Fanconi Anemia
Case-Control Studies
bioenergetic pathways
Zdroj: European Journal of Haematology
ISSN: 0902-4441
DOI: 10.1111/ejh.12131
Popis: Fanconi anaemia (FA) is a genetic cancer predisposition disorder associated with cytogenetic instability, bone marrow failure and a pleiotropic cellular phenotype, including low thresholds of responses to oxidative stress, cross-linking agents and selected cytokines. This study was aimed at defining the scope of abnormalities in gene expression using the publicly available FA Transcriptome Consortium (FTC) database (Gene Expression Omnibus, 2009 and publicly available as GSE16334). We evaluated the data set that included transcriptomal analyses on RNA obtained from low-density bone marrow cells (BMC) from 20 patients with FA and 11 healthy volunteers, by seeking to identify changes in expression of over 22,000 genes, including a set of genes involved in: (i) bioenergetic pathways; (ii) antioxidant activities; (iii) response to stress and metal-chelating proteins; (iv) inflammation-related cytokines and (v) DNA repair. Ontological analysis of genes expressed at magnitudes of 1.5-fold or greater demonstrated significant suppression of genes in the categories of (i) energy metabolism; (ii) antioxidant activities; and (iii) stress and chelating proteins. Enhanced expression was found for 16 of 26 genes encoding inflammatory cytokines. A set of 20 of 21 transcripts for DNA repair activities were down-regulated; four of these transcripts related to type II topoisomerase. The data provide evidence for alterations in gene regulation of bioenergetic activities, redox-related activities, stress and metal-chelating proteins, and of some selected DNA repair activities in patients with FA.
Databáze: OpenAIRE
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