Transcriptomic profile of ataxia telangiectasia cells treated for 30 days with a low dose of dexamethasone

Abstract

Dexamethasone administered by autologous red blood cells (RBCs) is used in clinical trials and as compassionate therapy to alleviate ataxia telangiectasia (AT) symptoms, providing long-term delivery of low doses of the drug. In the present paper, we report a dexamethasone-induced variation in gene expression that differed between healthy and AT primary fibroblasts simulating patient conditions. Gene expression levels were analysed by a microarray platform. The obtained gene-set data were used for biological pathway analysis by Reactome functional network clustering. Over 3000 probes were differentially modulated by dexamethasone in wild-type (WT) and AT fibroblasts. Consequently, the biological pathways induced by dexamethasone treatment also differed between the two samples. Some of the pathways were the same as those normally altered in AT compared to WT cells. Our results were consistent with earlier studies on HDAC4 and DDIT4 dynamics. The 30-day low dose dexamethasone treatment induced differential gene expression in AT and WT cells, leading to the partial recovery of genes that are usually dysregulated in AT. This is probably due to glucocorticoid receptor diversity in AT, which is likely genetically imprinted in AT, thus accounting for the differential response of AT cells to dexamethasone treatment.