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GSE70927
Homo sapiens
55 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate effects of tumor host interactions in vivo in CLL, purified tumor cells were obtained concurrently from blood, bone marrow and/or lymph node and analyzed by gene expression profiling.
Publication Title
The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.
Publication Title
Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment.
Publication Title
Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Immune stimulation contributes to lenalidomides anti-tumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T-cell function in vitro. Whether T-cell activation is required for clinical response to lenalidomide remains unclear. Here we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with anti-tumor response. Within days of starting lenalidomide, CD3+ cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pre-treatment and on-treatment lymph node biopsies revealed upregulation of IFN and many of its target genes in response to lenalidomide. The IFN-mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of T-cell receptor genes revealed decreasing diversity of the T-cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T-cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease stage, Subject, Compound
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology.
Publication Title
Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Room temperature whole blood mRNA stabilization procedures, such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable.
Publication Title
Characterization of whole blood gene expression profiles as a sequel to globin mRNA reduction in patients with sickle cell disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bone marrow-derived progenitor cells are under investigation for cardiovascular repair, but may be altered by disease. We identified 82 differentially expressed genes in CD133+ cells from patients with coronary artery disease (CAD) versus controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cellular development and signaling, molecular transport and cell differentiation. Following completion of an exercise program, gene expression patterns resembled those of controls in 7 of 10 patients.
Publication Title
Transcriptional profiling of CD133(+) cells in coronary artery disease and effects of exercise on gene expression.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective of this study is to identify the genes that are up-regulated amid proteasome dysfunction to facilitate the discovery of proteolytic pathways that are activated as a compensatory response to proteasome inhibition. Proteasome is a large multi-component proteolytic complex in the cell. It is responsible for the constitutive turn-over of many cellular proteins as well as the degradation of oxidized and/or unfolded proteins. With such a fundamental role in the cell, disruption of proteasome understandably can lead to disastrous outcome. Oxidative stress has been postulated as the driving mechanism for aging. Oxidatively modified proteins, which usually have lost their activity, require immediate removal by proteasome to maintain normal cellular function. Dysfunction of proteasome has also been linked to neuro-degenerative diseases such as Alzheimers and Parkinsons diseases, those that are most commonly seen in aged population. There is more than one proteolytic pathway in the cell, and it has been reported that obstruction of any one of these pathways may enhance the activity of the others. Proteasomal function has been found to have decreased during aging, prompting researchers to hypothesize that failure to remove oxidized proteins may play an important role in aging. It would be interesting to determine the other proteolytic pathways that are activated after proteasome inhibition by a relatively specific inhibitor epoxomicin to help understand their roles in aging processes.
Publication Title
Iron regulatory protein 2 turnover through a nonproteasomal pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Cells from 2 FL patients and 1 FL cell line were cultured for up to 48h, with no stroma or on top of HK cells pre-establised layers. RNA from FL cells was isolated after 24 and 48h of culture
Publication Title
Disruption of follicular dendritic cells-follicular lymphoma cross-talk by the pan-PI3K inhibitor BKM120 (Buparlisib).
Sample Metadata Fields
Cell line, Time
View Samples