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Series GSE57795 Query DataSets for GSE57795
Status Public on May 20, 2014
Title in vivo dexamethasone-induced gene expression in pediatric acute lymphoblastic leukemia patient-derived xenografts
Platform organism Homo sapiens
Sample organism Mus musculus
Experiment type Expression profiling by array
Summary Glucocorticoids are critical components of combination chemotherapy regimens in pediatric acute lymphoblastic leukemia (ALL). The pro-apoptotic BIM protein is an important mediator of glucocorticoid-induced apoptosis in normal and malignant lymphocytes, while the anti-apoptotic BCL2 confers resistance. The signaling pathways regulating BIM and BCL2 expression in glucocorticoid-treated lymphoid cells remain unclear. In this study, pediatric ALL patient-derived xenografts (PDXs) inherently sensitive or resistant to glucocorticoids were exposed to dexamethasone in vivo. In order to understand the basis for differential in vivo glucocorticoid sensitivity of PDXs, microarray analysis of gene expression was carried out on 5 each of dexamethasone-sensitive and resistant PDXs . This provided a global understanding of dexamethasone-induced signaling cascades in ALL cells in vivo, and especialy identified the genes that are involved in transducing the apoptotic signal, upstream of BIM/BCL2 dynamic interactions.
 
Overall design ALL xenograft cells were inoculated by tail-vein injection into NOD/SCID mice, and engraftment was monitored weekly. When >70% %huCD45+ engraftment in the peripheral blood was apparent, which occurred 8-10 weeks post-transplantation, mice were treated with either dexamethasone (15 mg/kg) or vehicle control by intra-peritoneal (IP) injection, and culled at 8 hours following the treatment. Cell suspensions of spleens were prepared and mononuclear cells enriched to >97% human by density gradient centrifugation. RNA was extracted using the RNeasy Mini Kit (QIAGEN, Valencia, CA, USA), and RNA samples with integrity number (RIN) > 8.0 were amplified and hybridized onto Illumina HumanWG-6 v3 Expression BeadChips (6 samples/chip). All chips (with associated reagents) were purchased from Illumina, and scanned on the Illumina BeadArray Reader according to the manufacturer’s instructions. Microarray data were analyzed using the online modules in GenePattern.
10 xenografts were derived from patients of 5 dexamethasone-good responder and 5 dexamethasone-poor responder. Each xenograft was innoculated into 5-6 mice, and treated with dexamethasone (15 mg/kg) or vehicle control. In total spleen-harvest xenograft samples from 58 mice were analyzed using microarray.
 
Contributor(s) Bhadri VA, Jing D, Lock RB
Citation(s) 25336632, 26960974, 27302164
Submission date May 19, 2014
Last update date Feb 18, 2019
Contact name Duohui Jing
E-mail(s) DJing@ccia.unsw.edu.au
Phone 0061 2 9385 1959
Organization name Children’s Cancer Institute Australia
Department Leukaemia Biology
Street address Lowy Cancer Research Centre, UNSW
City Randwick
State/province NSW
ZIP/Postal code 2031
Country Australia
 
Platforms (1)
GPL6884 Illumina HumanWG-6 v3.0 expression beadchip
Samples (58)
GSM1388640 ALL-26 control sample 1
GSM1388641 ALL-26 control sample 2
GSM1388642 ALL-26 8h Dex treatment sample 1
Relations
BioProject PRJNA248171

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
GSE57795_RAW.tar 6.3 Mb (http)(custom) TAR
GSE57795_non-normalized_data.txt.gz 11.3 Mb (ftp)(http) TXT
Processed data included within Sample table

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