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GSE85333
Homo sapiens
182 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
The direct communication between our central nervous and inflammatory signalling systems is a well-recognised, yet poorly understood relationship. To increase our understanding of this relationship, we examined the metabolism of serotonin and its precursor tryptophan in macrophages under inflammatory settings. Both are involved in inflammatory signalling and known to play a major role in mood regulation. Tryptophan depletion by macrophages during inflammation can consequently result in a reduction of serotonin systemically and has been suggested to cause depression. Increased understanding of this system could help overcome the problem of treatment resistant depressed patients. To this end, we treated primary human monocyte derived macrophages with a range of anti-depressant/anti-inflammatory drugs and analysed their transcriptional profile under various inflammatory conditions. In addition to the classic endotoxic driver of inflammation, LPS, we also used IFN which is a constitutive cytokine shown to directly induce depression when administered in high doses. The anti-depressant drugs were not found to have any significant effects on macrophage inflammatory signalling. However, the anti-inflammatories drugs were found to alter components of the serotonin/tryptophan metabolism pathways. This study increases our understanding of the intricacies of immune/mood cross-talk and offers into developing anti-inflammatories as co-treatment for depression.
Publication Title
Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study investigated gene expression changes in whole blood samples obtained from donors diagnosed with major depressive disorder (MDD) compared to healthy controls. Micro-array data were available from whole blood on patients with MDD (N=128, 64 with generalised anxiety disorder, diagnosed by the MINI questionnaire, and 64 without anxiety disorder) and healthy controls (N=64). RNA was isolated from all samples using the standard PAXgene protocol on the Qiagen Biorobot 8000. All samples gave good quality RNA, as assessed by Agilent Bioanalyser. The yield range was 0.86-15.05ug with an average of 6.25ug. Samples were then randomised into batches, with each batch containing a representative number of controls, depression with anxiety and depression without anxiety, and the same ratio of females to males (3:1). 50ng of RNA from each sample was converted to a biotin labeled cDNA probe using NuGEN SPIA amplification. The probes were then hybridized to Affymetrix U133_Plus2.0 Genechips.
Publication Title
Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 251 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute myeloid leukemia (AML) is a heterogeneous disease and AML with normal karyotype (AML-NK) is categorized as an intermediate-risk group. Over the past years molecular analyses successfully identified biomarkers that will further allow to dissecting clinically meaningful subgroups in this disease. Thus far, somatic mutations were identified which elucidate the disturbance of cellular growth, proliferation, and differentiation processes in hematopoietic progenitor cells. In AML-NK, acquired gene mutations with prognostic relevance were identified for FLT3, CEBPA, and NPM1. FLT3-ITD mutations were associated with short relapse-free and overall survival, while mutations in CEBPA or NPM1 (without concomitant FLT3-ITD) had a more favorable outcome.
Publication Title
Quantitative comparison of microarray experiments with published leukemia related gene expression signatures.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative mRNA splicing represents an effective mechanism of regulating gene function and is a key element to increase the coding capacity of the human genome. Today, an increasing number of reports illustrates that aberrant splicing events are common and functionally important for cancer development. However, more comprehensive analyses are warranted to get novel insights into the biology underlying malignancies like e.g. acute myeloid leukemia (AML). Here, we performed a genome-wide screening of splicing events in AML using an exon microarray platform. We analyzed complex karyotype and core binding factor (CBF) AML cases (n=64) in order to evaluate the ability to detect alternative splicing events distinguishing distinct leukemia subgroups. Testing different commercial and open source software tools to compare the respective AML subgroups, we could identify a large number of potentially alternatively spliced transcripts with a certain overlap of the different approaches. Selected candidates were further investigated by PCR and sequence analysis: out of 24 candidate genes studied, we could confirm alternative splice forms in 8 genes of potential pathogenic relevance, such as PRMT1 regulating transcription through histone methylation and participating in DNA damage response, and PTPN6, which encodes for a negative regulator of cell cycle control and apoptosis. In summary, this first large Exon microarray based study demonstrates that transcriptome splicing analysis in AML is feasible but challenging, in particular with regard to the currently available software solutions. Nevertheless, our results show that alternatively spliced candidate genes can be detected, and we provide a guide how to approach such analyses.
Publication Title
A robust estimation of exon expression to identify alternative spliced genes applied to human tissues and cancer samples.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored.
Publication Title
Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Oncogenic tyrosine kinases, such as BCR-ABL, TEL-ABL, TEL-PDGF-beta-R and FLT3-ITD, play a major role in the development of hematopoietic malignancy. They activate many of the same signal transduction pathways.
Publication Title
Id1 is a common downstream target of oncogenic tyrosine kinases in leukemic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thalidomide Exerts Distinct Molecular Antileukemic Effects and Combined Thalidomide/Fludarabine Therapy is Clinically Effective in High-Risk Chronic Lymphocytic Leukemia
Publication Title
Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Core binding factor (CBF) leukemias, characterized by translocations t(8;21) or inv(16)/t(16;16) targeting the core binding factor, constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, about 40% of patients relapse, and the current classification system does not fully reflect this clinical heterogeneity. Previously, gene expression profiling (GEP) revealed two distinct CBF leukemia subgroups displaying significant outcome differences and identified apoptotic signaling, MAPKinase signaling and chemotherapy-resistance mechanisms among the most significant differentially regulated pathways. We now tested different inhibitors of the respective pathways in a cell line model (six cell lines reflecting the CBF subgroup specific gene expression alterations), and found apoptotic signaling to be differentiating between the CBF subgroup models. In accordance, primary samples from newly diagnosed CBF AML patients (n=23) also showed differential sensitivity to in vitro treatment with a Smac mimetic such as BV6, an antagonist of inhibitor of apoptosis (IAP) proteins , and ABT-737, a BCL2 inhibitor. Furthermore, GEP revealed the BV6 resistant cases to resemble the previously identified unfavorable CBF subgroup. Thus, our current findings show deregulated IAP expression and apoptotic signaling to differentiate clinically relevant CBF subgroups, which were independent of known molecular markers, thereby providing a starting point for novel therapeutic approaches.
Publication Title
Deregulated apoptosis signaling in core-binding factor leukemia differentiates clinically relevant, molecular marker-independent subgroups.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The aim of the study was to investigate the role of TGIF1 in MLL-AF9 transformed cells
Publication Title
TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
Specimen part
View Samples