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Status |
Public on Nov 28, 2011 |
Title |
The NOD/SCID Xenograft Model Provides Clinically-Relevant Insights into Glucocorticoid-Induced Gene Expression in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Introduction. Glucocorticoids are critical drugs used to treat acute lymphoblastic leukemia, and response to glucocorticoids is highly predictive of outcome. Here we report a study evaluating the NOD/SCID xenograft mouse model to investigate glucocorticoid-induced gene expression. Methods. NOD/SCID mice were inoculated with ALL-3, a glucocorticoid-sensitive xenograft, and when highly engrafted were randomised to either dexamethasone 15mg/kg or vehicle control IP. Cells were harvested at 0, 8, 24 or 48 hours thereafter, RNA was extracted and hybridised onto Illumina WG-6_V3 chips. Results. The 8 hour dexamethasone-treated timepoint had the highest number of significantly differentially expressed genes with minimal changes seen across the time-matched controls. Replicate analysis revealed that using data from 3 replicates instead of 4 resulted in excellent recovery scores of >0.9 at timepoints with high signal. When assessed at the level of pathways, gene expression changes in the 8 hour xenograft samples were similar to patients treated with glucocorticoids. Conclusions. The NOD/SCID xenograft mouse model provides a reproducible experimental model system in which to investigate clinically-relevant mechanisms of in vivo glucocorticoid-induced gene regulation in ALL; the 8 hour timepoint provides the highest number of significantly differentially expressed genes; time-matched controls are redundant and excellent recovery scores can be obtained with 3 replicates.
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Overall design |
At 0, 8, 24 or 48 hours, NOD/SCID xenograft mice were treated with vehicle control, or dexamethasone. We used 4 biological replicates per time point (3 at the 48hour time point), each of which went onto an Illumina HumanWG-6_V3_0_R1_11282955_A microarray. Samples from each of the 7 groups were divided across a total of 5 microarray slides
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Contributor(s) |
Bhadri VA, Cowley MJ, Kaplan W, Trahir TN, Lock RB |
Citation(s) |
22093874 |
Submission date |
Jul 05, 2011 |
Last update date |
Feb 18, 2019 |
Contact name |
Vivek A Bhadri |
E-mail(s) |
vbhadri@ccia.unsw.edu.au
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Organization name |
Children's Cancer Institute Australia for Medical Research
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Department |
Leukaemia Biology Program
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Street address |
Lowy Cancer Research Centre
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City |
Randwick |
State/province |
NSW |
ZIP/Postal code |
2031 |
Country |
Australia |
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Platforms (1) |
GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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Samples (26)
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Relations |
BioProject |
PRJNA143443 |