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Series GSE15490 Query DataSets for GSE15490
Status Public on Mar 01, 2011
Title Sequential gene expression profiling in CLL during treatment
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Purpose:
Accurate prediction of clinical response is the prerequisite for individualized therapy in chronic lymphocytic leukemia (CLL). We hypothesized that sequential assessment of gene expression changes early during therapy may well reflect behaviour of the leukemic clone in response to specific drugs.
Patients and Methods: Gene expression profiles (GEP) were determined in CD19+ selected B-cells from 20 patients treated with fludarabine and cyclophosphamide (FC) (N=10) or FC plus rituximab (FCR) (N=10). Samples were collected in the first cycle before and within 48hours after initiation of treatment. GEP analysis was stratified by clinical response 3 months after start of therapy.
Results: GEP before treatment detected high expression of 34 genes correlated with response and 32 genes correlated with resistance to therapy. These genes were related to regulation of apoptosis, cell cycle, cell adhesion, and signal transduction. Different results were obtained with sequential GEP: Sixteen genes were up-regulated after rituximab infusion in non-responders. Rituximab therapy resulted in down-regulation of AKT1 indicating involvement of the PI3-kinase pathway in CD20-signaling. Up-regulation of 24 genes after FC (including ITPKB (inositol 1,4,5-trisphosphate 3-kinase) and CD44) and of 36 genes after FCR (including CD49d) was associated with resistance. Down-regulation of CTLA4 correlated with poor response to FC. CD44, CD49d and the PI3-kinase signaling pathway were confirmed as potential therapeutic targets to overcome resistance by (protein analysis) or functional experiments. Conclusion Sequential GEP provides rapid and relevant information for prediction of response and resistance. This approach could be used to guide and adapt individualized therapy in CLL.
 
Overall design 50 Samples from CD19 selected B-cells, three treatments (rituximab, FC and RFC), 10 replicates for each treatment, 20 replicates for control condition
 
Contributor(s) Shehata M, Tauber S, Bilban M, Jaeger U
Citation(s) 20966934
Submission date Apr 01, 2009
Last update date Mar 25, 2019
Contact name Stefanie Tauber
E-mail(s) stefanie.tauber@univie.ac.at
Organization name MFPL
Department CIBIV
Street address Dr. Bohr-Gasse 9
City Vienna
ZIP/Postal code 1030
Country Austria
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (50)
GSM388583 CD19_selected_B-cells_before_R_rep1
GSM388584 CD19_selected_B-cells_before_R_rep2
GSM388585 CD19_selected_B-cells_before_R_rep3
Relations
BioProject PRJNA115937

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
GSE15490_RAW.tar 240.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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