Expression data from glucocorticoid-treated ALL (CCRF-CEM-C7-14 cells)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Daphne Chen
PROVIDER: E-GEOD-39338 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.
Chen D W-C DW Saha V V Liu J-Z JZ Schwartz J-M JM Krstic-Demonacos M M
Oncogene 20120806 25
Glucocorticoids (GCs) are among the most widely prescribed medications in clinical practice. The beneficial effects of GCs in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis, but the underlying transcriptional mechanisms remain poorly defined. Computational modeling has enormous potential in the understanding of biological processes such as apoptosis and the discovery of novel regulatory mechanisms. We here present an integrated analysis of gene expression kinet ...[more]
Similar Datasets
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed. We performed micro-RNA on two different bortezomib resistant subclones of the CCRF-CEM cell line. The resistant subclones were compared to the parental CCRF-CEM wildtype cell line.
2015-11-04 | E-GEOD-74632 | biostudies-arrayexpress
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed. We performed comparative Genome hybridization (arrayCGH) for DNA copy number analysis on four different bortezomib resistant subclones of the CCRF-CEM cell line. The resistant subclones were compared to the parental CCRF-CEM wildtype cell line and reference DNA.
2015-11-04 | E-GEOD-74633 | biostudies-arrayexpress
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed. We performed gene expression microarray analysis on four different bortezomib resistant subclones of the CCRF-CEM cell line. The resistant subclones were compaired to treated and untreated the parental CCRF-CEM wildtype cell line.
2015-11-04 | E-GEOD-74634 | biostudies-arrayexpress
Project description:Background: Glucocorticoids are important pharmaceutical agents in the treatment of acute lymphoblastic leukemia in children. Resistance or sensitivity to glucocorticoids is considered to be of crucial importance for disease prognosis. Prednisolone is a first-line chemotherapeutic agent in the treatment of acute lymphoblastic leukemia. Here, the effects of prednisolone on the resistant CCRF-CEM leukemic cell line were studied. Methods: Prednisolone’s cytotoxic and cell cycle effects were studied with flow cytometry. NF-κB translocation was studied with Western Blotting and differential gene expression was studied with cDNA microarrays. Results: Prednisolone exerted a delayed biphasic effect, necrotic at low doses and apoptotic at higher doses. At low doses, prednisolone exerted a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone’s mitogenic and cell death effects were counterbalanced. NF-κB was constitutively present in the nucleus. Early gene microarray analysis revealed 40 differentially expressed genes upon 4 hours of prednisolone’s exposure. Notable differences in gene regulation were observed between the lowest and the highest glucocorticoid doses. Prednisolone activated genes related to apoptosis/tumor suppression, cell cycle progression, metabolism and intra-/ extra-cellular signaling pathways. Conclusions: The mitogenic/biphasic effects of prednisolone are of clinical importance in the case of resistant leukemic cells. This approach might lead to the identification of gene candidates for future molecular drug targets in combination therapy with glucocorticoids, along with early markers for glucocorticoid resistance. Elucidation of the mechanisms of GC action may lead to identification of gene targets responsible for GC resistance. Key tools in this process are high-throughput technologies such as microarray-based gene expression analysis. For this purpose, the parental CCRF-CEM cell line was chosen as the system of study for the effects of prednisolone treatment. This is a T-cell leukemia cell line characterized by a mutation (L753F) on one GR gene allele that impairs ligand binding (Thompson and Johnson 2003). It is known that both the DNA and ligand binding domains of the GR are required in order to repress NF-κB transactivation (Wissink, van Heerde et al. 1997). Interestingly, concerning the question whether this mutation would affect GC resistance, it has been reported previously that both the GC-resistant as well as the GC-sensitive CCRF-CEM subclones express heterogeneous populations of the GR (GRwt/GRL753F) (Palmer and Harmon 1991; Powers, Hillmann et al. 1993). The CCRF-CEM cell line has been reported to be resistant to GCs, presumably due to the accumulation of more resistant variants after long periods of prolonged culture (Norman and Thompson 1977). It is possible that these cells are clonally inhomogeneous, as possibly the cells obtained in vivo by patients. Moreover, the large number of the CCRF-CEM subclone studies in the literature makes it difficult to choose an appropriate resistant cell model. In addition, the utilization of an in vitro system for this study offered reproducibility, an opportunity to closely examine intracellular signals and avoid interference from other in vivo-participating systems. Thus, the cell line used for this study was considered to be useful in studying GC action and resistance in leukemic cells. The aim of this work was to determine the cytotoxic, cell cycle phase distribution and early cancer-specific gene expression effects of prednisolone in CCRF-CEM cells, as an in vitro model of ALL resistance to glucocorticoids. The early gene expression profile allowed identification of genes initiating pivotal, early onset regulatory mechanisms activated by GC and excluded ensuing feedback responses and further downstream signals. Samples tested were in the form of a loop-design i.e. control vs. 10nM prednisolone (designated 0vs1) , 10nM prednisolone vs.700uM prednisolone (designated 1vs3) and control vs. 700uM prednisolone (designated 0vs3), the sum of the logarithms of the first two should equal the third. In other words if Rj,i is the ratio of the ith gene in the jth experiment then R0vs1,i+R1vs3,i=R0vs3,i. We tested this using a statistical test. We have applied an intensity-dependent z-score where the sum of the ratios was compared to the ratio of the third experiment. If the difference was significant genes, in a standard deviation threshold of ±1.5 in relative units, were rejected from further analysis (Kerr and Churchill 2001; Kerr and Churchill 2001; Altman and Hua 2006; Kerr and Churchill 2007).
2011-03-22 | E-GEOD-27989 | biostudies-arrayexpress
Project description:It has been shown previously that glucocorticoids exert a dual mechanism of action, entailing cytotoxic, mitogenic as well as cell proliferative and anti-apoptotic responses, in a dose-dependent manner on CCRF-CEM cells at 72 h. Early gene expression response implies a dose-dependent dual mechanism of action of prednisolone too, something reflected on cell state upon 72 h of treatment. In this work, a generic, computational microarray data analysis framework is proposed, in order to examine the hypothesis whether CCRF-CEM cells exhibit an intrinsic or acquired mechanism of resistance and to investigate the molecular imprint of this, upon prednisolone treatment. The experimental design enables the examination of both the dose (0 nM, 10 nM, 22 uΜ, 700 uΜ) effect of glucocorticoid exposure and the dynamics (early and late, namely 4 h, 72 h) of the molecular response of the cells at the transcriptomic layer. In this work we demonstrated that CCRF-CEM cells may attain a mixed mechanism of response to glucocorticoids, however, there is clear evidence predicating towards an intrinsic mechanism of resistance. More specifically, at 4 h prednisolone appeared not to perform its expected function by down-regulating apoptotic genes, which is re-enforced by mechanisms, which down-regulate other sets of apoptotic genes. Also, low and high prednisolone concentrations up-regulates metabolic and signal-transduction related genes in both time points, thus grounding for a cell proliferation machinery. In addition, regulation of NF-κB-related genes implies an inherent mechanism of resistance through the established link of NF-κB inflammatory role and GC-induced resistance. The analysis framework applied here allows derivation of regulatory mechanisms activated by prednisolone through identification of early responding sets of genes. On the other hand, study of the prolonged exposure to glucocorticoids (72 h exposure) highlights the effect of homeostatic feedback mechanisms of the treated cells. Overall, it appears that CCRF-CEM cells in this study exhibit a diversified, combined pattern of intrinsic and acquired resistance to prednisolone, yet with a tendency towards inherent resistant characteristics, through activation of different molecular courses of action.
2011-03-26 | GSE28154 | GEO
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). The published data used were as follows: GSE2677: GSM51674: B-ALL-24-24h GSM51675: B-ALL-24-6h GSM51676: B-ALL-24-0h GSM51680: B-ALL-17-24h GSM51681: B-ALL-17-8h GSM51682: B-ALL-17-0h GSM51677: B-ALL-13-24h GSM51678: B-ALL-13-8h GSM51679: B-ALL-13-0h GSM51683: B-ALL-31-24h GSM51684: B-ALL-31-6h GSM51685: B-ALL-31-0h GSM51686: B-ALL-32-24h GSM51687: B-ALL-32-6h GSM51688: B-ALL-32-0h GSM51689: B-ALL-33-24h GSM51690: B-ALL-33-6h GSM51691: B-ALL-33-0h GSM51692: B-ALL-37-24h GSM51693: B-ALL-37-6h GSM51694: B-ALL-37-0h GSM51695: B-ALL-38-24h GSM51696: B-ALL-38-6h GSM51697: B-ALL-38-0h GSM51698: B-ALL-40-24h GSM51699: B-ALL-40-6h GSM51700: B-ALL-40-0h GSM51701: B-ALL-43-24h GSM51702: B-ALL-43-6h GSM51703: B-ALL-43-0h GSM51707: T-ALL-25-24h GSM51708: T-ALL-25-6h GSM51709: T-ALL-25-0h GSM51704: T-ALL-20-24h GSM51705: T-ALL-20-8h GSM51706: T-ALL-20-0h GSM51710: T-ALL-2-24h GSM51711: T-ALL-2-8h GSM51712: T-ALL-2-0h GSE2842 GSM60545: S-Line-PreB-6h-EtOH GSM60546: S-Line-PreB-6h-GC GSM60547: S-Line-PreB-24h-GC GSM60542: S-Line-C7H2-6h-EtOH GSM60543: S-Line-C7H2-6h-GC GSM60544: S-Line-C7H2-24h-GC GSM60560: R-Line-CEMC1-6h-EtOH GSM60561: R-Line-CEMC1-6h-GC GSM60562: R-Line-CEMC1-24h-GC GSM60564: R-Line-C7R1-6h-EtOH GSM60566: R-Line-C7R1-6h-GC GSM60576: R-Line-C7R1dim-low-6h-EtOH GSM60578: R-Line-C7R1dim-low-6h-GC GSM60579: R-Line-C7R1dim-low-24h-GC GSM60581: R-Line-PreB-6h-EtOH GSM60583: R-Line-PreB-6h-GC GSM60584: R-Line-PreB-24h-EtOH GSM60586: R-Line-PreB-24h-GC GSM60548: C-Line-CEMC1-ratGR-6h-EtOH GSM60549: C-Line-CEMC1-ratGR-6h-GC GSM60550: C-Line-CEMC1-ratGR-24h-GC GSM60551: C-Line-C7R1dim-high-6h-EtOH GSM60552: C-Line-C7R1dim-high-6h-GC GSM60553: C-Line-C7R1dim-high-24h-GC
2012-09-01 | GSE39338 | GEO
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.
2012-09-01 | E-GEOD-39335 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE39335: Expression data from glucocorticoid-treated ALL (BCR-ABL patients) GSE39338: Expression data from glucocorticoid-treated ALL (CCRF-CEM-C7-14 cells) Refer to individual Series
2012-09-01 | E-GEOD-39339 | biostudies-arrayexpress
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed.
2015-11-04 | GSE74634 | GEO
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed.
2015-11-04 | GSE74633 | GEO