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Series GSE89231 Query DataSets for GSE89231
Status Public on Oct 27, 2019
Title Doxorubicin response in diffuse large B-cell lymphoma cell lines varies with concentration, exposure duration, and level of intrinsic sensitivity
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Although diffuse large B-cell lymphoma (DLBCL) is a very heterogeneous disease, patients are as standard treated with a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Since approximately 40% of patients die due to refractory disease or relapse, enhanced knowledge about drug response mechanisms is required to improve treatment outcome. Therefore, this study assesses parameters that possibly influence doxorubicin response. Doxorubicin-induced impact on the number of living cells was evaluated for four human DLBCL cell lines, illustrating differences in intrinsic sensitivity levels. Six cell lines were subjected to gene expression profiling upon exposure to two distinct drug concentrations (0.00061 μg/mL and 2.5 μg/mL) for 2, 12, and 48 hours. Variation in gene expression compared to baseline was determined with a mixed-effects model, and gene ontology enrichment analysis was performed using the webtools GOrilla and REVIGO. Only few genes were differentially expressed after short exposure and/or exposure to the low concentration, suggesting lack of drug efficacy under these conditions. In contrast, 12-hour exposure to the high concentration induced several changes. In sensitive cell lines, doxorubicin affected the expression of genes involved in ncRNA metabolism, DNA repair, and cell cycle process mechanisms. In resistant cell lines, the expression of genes implicated in metabolic processes were altered. Thus, we observed a differential response rate to doxorubicin in distinct DLBCL cell lines and demonstrated that doxorubicin-induced alterations in gene expression and resulting ontologies vary with drug concentration, exposure duration, and intrinsic sensitivity level.
 
Overall design Global gene expression data of DLBCL cell lines untreated or after 2, 12, and 48 hours of exposure to two distinct concentrations (0.00061 μg/mL and 2.5 μg/mL) of doxorubicin.
 
Contributor(s) Marques SC, Reinholdt L, Bødker JS, Schmitz A, Mikkelsen JG, Johnsen HE, Bøgsted M, Dybkær K
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Submission date Oct 27, 2016
Last update date Oct 29, 2019
Contact name Julie Støve Bødker
E-mail(s) j.boedker@rn.dk
Organization name Aalborg University Hospital
Department Department of Heamatology
Lab Research Laboratory
Street address Sdr. Skovvej 15
City Aalborg
ZIP/Postal code 9000
Country Denmark
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (49)
GSM2361446 FARAGE-No doxorubicin exposure-0ug/mL-0h
GSM2361447 FARAGE-Doxorubicin exposure-2.5ug/mL-12h
GSM2361448 FARAGE-Doxorubicin exposure-0.00061ug/mL-12h
Relations
BioProject PRJNA350787

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE89231_RAW.tar 223.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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