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

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RESEARCH PRODUCT

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

Sandra Petrović Luca Tiano Giovanni Pagano Beatriz Porto Annarita Aiello Talamanca Federico V. Pallardó Giuseppe Castello Marco D'ischia Adriana Zatterale

subject

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 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 Transcriptome

description

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.

year	journal	country	edition	language
2013-01-01	European Journal of Haematology

https://doi.org/10.1111/ejh.12131