LncRNA Expression Discriminates Karyotype and Predicts Survival in B-lymphoblastic Leukemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dinesh Rao
PROVIDER: E-GEOD-65647 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Long non-coding RNAs (lncRNAs) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by RT-qPCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. To define gene expression changes attributable to expression of lncRNAs, we transduced RS4;11 cells with a siRNA against BALR-2 or control vector. These cells were left untreated or treated with prednisolone.
2015-02-05 | E-GEOD-65646 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by RT-qPCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B-cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. B-lymphoblastic leukemia is characterized by several translocations. In this study, we hybridized patient bone marrow samples from a total of 44 patients including 14 patients with B-ALL carrying a TEL-AML1 translocation, 15 patients with E2A-PBX1 translocation, and 15 patients carrying MLL translocations. The hybridizations were carried out in two sets, a discovery set and a validation set. In addition, we utilized samples from a human cell line (NALM6) and control CD10+CD19+ cells from human bone marrow.
2015-02-05 | E-GEOD-65645 | biostudies-arrayexpress
Project description:Muscle biopsies taken from vastus lateralis muscle of 30 normal subjects and 19 FSHD subjects (see PubMed ID 17151338); Affymetrix U133A and U133B arrays were scanned both before (S1) and after (S2) antibody enhancement. Effects of age and sex in normal subjects reported previously under GSE362, GSE674, and GSE9676. Experiment Overall Design: Gene expression profiles were generated for each individual for a total of 49 profiles (30 normal, 19 FSHD)
2008-04-06 | E-GEOD-10760 | biostudies-arrayexpress
Project description:In order to characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we compared gene expression in uncultured amniotic fluid supernatant samples. We identified individually differentially expressed genes via paired t-tests in the matched samples, and a set of differentially expressed genes on chromosome 21 using Gene Set Enrichment Analysis. Functional pathway analysis of the resulting genes highlighted the importance of oxidative stress, ion transport, and G-protein signaling in the DS fetuses. We profiled seven DS expression samples and seven controls matched for gender and approximate gestational age..
2009-05-21 | E-GEOD-16176 | biostudies-arrayexpress
Project description:Background: The combination of Proteasome inhibitor with Glucocorticoid is one of the most promising antileukemic treatments. Both agents act through pluripotent signal mediators. The two types of agents inhibit key signals that are considered crucial to their effects on malignant cells. Methodology/Principal Findings: Combined use of the two reagents on the lymphoblastic leukemia cell line CCRF-CEM has a range of effects on the viability that depend on the dose and the time used. Even though both reagents are capable of enhancing cell death on the CEM cell line, no combinatorial increase in cell death is detectable, until after the first 120 hours of treatment. In contrast, there are a number of combinatorial effects on the cell cycle phase distribution of treated cells, which indicates a potential for mutual signal disruption between glucocorticoid and proteasome inhibitor at multiple levels. Microarray analysis indicates that Prednisolone and MG132 elicit highly divergent, early-response molecular signatures on this cell line. We assayed levels of the antiapoptotic protein Mcl-1 as a potential model of late, downstream target regulation by both glucocorticoid and proteasome. Synchronized use of Prednisolone with MG132 results in temporary stabilization of Mcl-1 in CEM cells. Stabilization is not the result of a common mechanism of action on the genome, as Prednisolone and MG132 elicit nonreduntant molecular signatures, and it occurs also when the cells are treated at different timepoints with either agent. Conclusions/Significance: Our results show that this glucocorticoid-resistant ALL lymphoblast line is highly sensitive to proteasome inhibitor, and suggest that the proteasome inhibitor and the glucocorticoid regulate different direct target genes. This difference in immediate targets, when the two agents are applied in combination, may lead to negative or positive interference with mechanisms regulating viability of the leukemic lymphoblast. Signal interference between glucocorticoid Prednisolone and the proteasome inhibitor MG132 is expected to occur at more than one level, resulting in complex effects on intracellular signal transduction pathways. The net result depends on the development of individual downstream effects and interactions between key signal mediators. Elucidation of the conditions of interference between glucocorticoid and proteasome targets on leukemic cell fate is expected to improve effects of applied treatment combinations. Experimental setups consisted of the three following samples obtained after 4 h treatment: control, 10nM prednisolone, 1uM prednisolone, 10uM prednisolone, 100M-NM-<M prednisolone, 700M-NM-<M prednisolone, 200nM MG132, 2M-NM-<M MG132 and 20M-NM-<M MG132. Untreated cells were used as reference.
2011-05-11 | E-GEOD-29136 | biostudies-arrayexpress
Project description:To understand the molecular mechanisms underlying the congenital anomalies observed in patients with Trisomy 18, we compared gene expression in uncultured amniotic fluid supernatant samples from second trimester fetuses with Trisomy 18 and from euploid controls. Analysis of differential expression using both individual-gene and gene-set or pathway methods indicated disrupted function in ion transport, MHCII/T-cell mediated immunity, DNA repair, G-protein mediated signaling, kinases, and glycosylation. Significant down-regulation of genes involved in adrenal development was also identified in the trisomic fetuses, possibly explaining both the abnormal maternal serum estriols and the pre- and postnatal growth restriction found in this condition. We compared expression in five female fetuses with confirmed metaphase karotypes 47, XX, +18 and six female controls (46, XX). The gestational ages of the samples ranged from 17 5/7 to 20 6/7 weeks.
2010-12-03 | E-GEOD-25634 | biostudies-arrayexpress
Project description:Discrimination of rheumatoid arthritis (RA) patients from patients with other inflammatory/degenerative joint diseases or healthy individuals purely on the basis of genes differentially expressed in high-throughput data has proven very difficult. Thus, the present study sought to achieve such discrimination by employing a novel unbiased approach using rule-based classifiers. Three multi-center genome-wide transcriptomic data sets (Affymetrix HG- U133 A/B) from a total of 79 individuals, including 20 healthy controls (control group - CG), as well as 26 osteoarthritis (OA) and 33 RA patients, were used to infer rule- based classifiers to discriminate the disease groups. The rules were ranked with respect to Kiendl’s statistical relevance index, and the resulting rule set was optimized by pruning. The rule sets were inferred separately from data of one of three centers and applied to the two remaining centers for validation. All rules from the optimized rule sets of all centers were used to analyze their biological relevance applying the software Pathway Studio. The optimized rule sets for the three centers contained a total of 29, 20, and 8 rules (including 10, 8, and 4 rules for ‘RA’), respectively. The mean sensitivity for the prediction of RA based on six center-to-center tests was 96% (range 90% to 100%), that for OA 86% (range 40% to 100%). The mean specificity for RA prediction was 94% (range 80% to 100%), that for OA 96% (range 83.3% to 100%). The average overall accuracy of the three different rule-based classifiers was 91% (range 80% to 100%). Unbiased analyses by Pathway Studio of the gene sets obtained by discrimination of RA from OA and CG with rule-based classifiers resulted in the identification of the pathogenetically and/or therapeutically relevant interferon-gamma and GM-CSF pathways. First-time application of rule-based classifiers for the discrimination of RA resulted in high performance, with means for all assessment parameters close to or higher than 90%. In addition, this unbiased, new approach resulted in the identification not only of pathways known to be critical to RA, but also of novel molecules such as serine/threonine kinase 10. Three multi-center genome-wide transcriptomic data sets (Affymetrix HG- U133 A/B) from a total of 79 individuals, including 20 healthy controls (control group - CG), as well as 26 osteoarthritis (OA) and 33 RA patients, were used to infer rule- based classifiers to discriminate the disease groups. The rules were ranked with respect to Kiendl’s statistical relevance index, and the resulting rule set was optimized by pruning. The rule sets were inferred separately from data of one of three centers and applied to the two remaining centers for validation. All rules from the optimized rule sets of all centers were used to analyze their biological relevance applying the software Pathway Studio.
2014-03-05 | E-GEOD-55457 | biostudies-arrayexpress
Project description:Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we show that an inverted version of WB allows parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS). The pipeline provides means for large-scale implementation of concepts proposed by an international working group on antibody validation (IWGAV).
2018-07-26 | PXD010510 | Pride
Project description:Amniotic fluid (AF) is a complex biological material that provides a unique window into the developing human. Residual AF supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the AF core transcriptome by identifying the transcripts ubiquitously present in the AF supernatant of euploid midtrimester fetuses. We detected 476 well-annotated genes present in all twelve AF samples. Functional analysis identified 6 physiological systems represented in the AF core transcriptome, including musculoskeletal and nervous system development and function and embryonic/ organismal development. mTOR signaling was identified as a key canonical pathway. Twenty-three highly organ-specific transcripts were identified; six of these are known to be highly expressed by fetal brain. This study demonstrates that AF cell-free fetal RNA can provide biological information about multiple fetal organ systems. This was an in silico investigation of gene expression in 12 euploid midtrimester AF samples acquired primarily for advanced maternal age. We focused on the transcripts called M-bM-^@M-^\presentM-bM-^@M-^] in all of the samples. Functional analyses were performed using Ingenuity software. Fetal-organ specificity was examined for each transcript using the GNF Gene Expression Atlas. For fetal organs not represented in the atlas, manual literature searching and Ingenuity analysis were used.
2012-01-11 | E-GEOD-33168 | biostudies-arrayexpress
Project description:Bacteria are extremely versatile organisms which rapidly adapt to changing environments. When Escherichia coli cells switch from planktonic growth to biofilm, flagellum formation is turned off, and the production of fimbriae and extracellular polysaccharides is switched on. Here we show that BolA protein is a new bacterial transcription factor which modulates the switch from planktonic to sessile lifestyle. BolA negatively modulates flagella biosynthesis and thus swimming capacity. Furthermore, BolA overexpression favors biofilm formation and involvesinvolving fimbriae-like adhesins and curli production. Our results unraveled for the first time that BolA is a protein with high affinity to DNA, involved in the regulation of several genes of E. coli at a genome-wide scale level. Moreover, this observation further demonstrated that the most significant targets of this protein involved a complex network of genes encoding proteins extremely necessary in biofilm development processes. Herein we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation process. In the study presented here mRNA levels were analyzed in 2 different strains with different levels of BolA protein. Samples were measured at two differet growth phases and include 3 replicates of each.
2015-02-19 | E-GEOD-58509 | biostudies-arrayexpress