Expression data from glucocorticoid-treated ALL
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Daphne Chen
PROVIDER: E-GEOD-39339 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The beneficial effects of glucocorticoids (GCs) in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis. Omics technologies such as DNA microarray analysis are widely used to study the changes in gene expression and have been successfully implemented in biomarker identification. In addition, time series studies of gene expression enable the identification of correlations between kinetic profiles of glucocorticoid receptor (GR) target genes and diverse modes of transcriptional regulation. This study presents a genome-wide microarray analysis of both our and published Affymetrix HG-U133 Plus 2.0 data in GCs-sensitive and -resistant ALL. GCs-sensitive CCRF-CEM-C7-14 cells were treated with dexamethasone at three time points (0 h, 2 h and 10 h). The treated samples were then compared to the control (0 h). Arrays were obtained from 10 children with Philadelphia positive (Ph+) ALL treated uniformly. They were categorized as good risk if the marrow had <25% blasts after 8 days of therapy without imatinib and poor risk if the blast count was >25%. During this time they received 8 days of Dex and 1 dose each of anthracycline, vincristine and L-Asparaginase, according to the EsphALL protocol. The samples were analysed at day 17 and compared to the untreated (day 0) samples.
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Project description:The efficacy of glucocorticoid receptor modulation is well established in Acute Lymphoblastic Leukemia(ALL) but the response remains heterogeneous and limited by emergence of drug resistance. Here we use, two clonally-derived cell lines (CEM-C1 and CEM-C7) from a 3-year-old T-cell ALL patient, as a model system to understand the mechanisms of drug resistance in these cell lines; the clone CEM-C1 is resistant to dexamethasone-induced apoptosis and CEM-C7 is sensitive. We performed ATACseq and RNAseq to query for TF binding motifs present in the open regions of the chromatin and expression levels of TFs that could recognize the identified motifs. We are experimentally validating our hypothesis that depletion of the TFs identified, either singly or in combination, in CEM-C7 cells will cause dexamethasone resistance in CEM-C7 cells.
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