Transcriptomics

Dataset Information

0

The NOD/SCID Xenograft Model Provides Clinically-Relevant Insights into Glucocorticoid-Induced Gene Expression in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia


ABSTRACT: 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. 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

ORGANISM(S): Homo sapiens  

SUBMITTER: Vivek A Bhadri   Richard B Lock  Mark J Cowley  Toby N Trahir  Warren Kaplan 

PROVIDER: E-GEOD-30392 | ArrayExpress | 2011-11-28

SECONDARY ACCESSION(S): GSE30392PRJNA143443

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Evaluation of the NOD/SCID xenograft model for glucocorticoid-regulated gene expression in childhood B-cell precursor acute lymphoblastic leukemia.

Bhadri Vivek A VA   Cowley Mark J MJ   Kaplan Warren W   Trahair Toby N TN   Lock Richard B RB  

BMC genomics 20111117


BACKGROUND: Glucocorticoids such as prednisolone and dexamethasone are critical drugs used in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL), and response to glucocorticoids is highly predictive of outcome. The NOD/SCID xenograft mouse model of ALL is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report a study evaluating the NOD/SCID xenograf  ...[more]

Similar Datasets

2014-12-18 | E-GEOD-58266 | ArrayExpress
| GSE58266 | GEO
2014-05-20 | E-GEOD-57795 | ArrayExpress
2011-11-09 | GSE33562 | GEO
2011-11-09 | E-GEOD-33562 | ArrayExpress
2017-05-01 | E-MTAB-4759 | ArrayExpress
| GSE51000 | GEO
| GSE50998 | GEO
2009-04-10 | E-GEOD-11184 | ArrayExpress
2014-01-08 | E-GEOD-52106 | ArrayExpress