Filters
Technology
Platform
GSE36036
Homo sapiens
31 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background. Multiple myeloma (MM) cells depend on the bone marrow (BM) niche for growth and survival. However, the tumor genes regulated by the niche are largely unknown.
Publication Title
Niche-modulated and niche-modulating genes in bone marrow cells.
Sample Metadata Fields
Disease, Disease stage, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression profile (GEP) was analyzed in bone marrow (BM) samples from patients with leukemia or leukemic phase of lymphoma at different time points following aspiration. Among numerous changes in GEP evolved over time a discrete subset of > 60 genes exhibited prompt and sustained switch in expression consistently. Similar results were discovered recently in BM samples from patients with multiple myeloma (GSE36036). GEP was also examined in peripheral blood as well as in BM samples depleted of red blood cells (=WBC) and in cultured cells from some of the patients.
Publication Title
Niche-modulated and niche-modulating genes in bone marrow cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Acute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
Publication Title
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 41 Downloadable Samples
- Illumina HiSeq 4000
Description
The rate of RNA Polymerase II (RNAPII) elongation has an important role in the control of Alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked-in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice and impairs the differentiation of ESCs into the neural lineage. This is accompanied by changes in splicing and in gene expression in ESCs and along the pathway of neuronal differentiation. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is more predominant in ESC-differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development. Overall design: 4sURDB-Seq mouse wt and homozygous Polr2a[R749H] mutant embryonic stem cells in triplicates.
Publication Title
A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cdh1 regulates not only mitotic phase and G1 phase, but also G2 checkpoint under irradiation-induced DNA damage. Despite several reports indicating its potential as tumor suppressor, how Cdh1 affects tumorigenesis or tumor progression and its clinical implementation has yet to be evaluated. Considering the pivotal role of Cdh1 on DNA repair, we hypothesized that Cdh1 loss also causes fragility of tumor cells to DNA damage under oncogenic stress or chemotherapy. To test this hypothesis, we established a Cdh1 gene-trapped B cell acute lymphoblastic leukemia (B-ALL) mouse model. Cdh1-deficient B-ALL mice survived longer than Cdh1-intact group, with higher susceptibility to DNA damage. Consistently, reverse phase protein array-based analysis of more than 200 human adult B-ALL samples showed that low Cdh1 was associated with high complete remission rates and long remission durations. Furthermore, the clinical benefit with lower Cdh1 expression diminished after relapse, supported by mouse experiments showing that secondary/tertiary transplants of Cdh1-deficient B-ALL cells developed more progressive/resistant disease than Cdh1-intact group. This indicated that prolonged inactivation of Cdh1 eventually develops resistant clones. Our results collectively demonstrated that Cdh1 is a potential predictive biomarker of B-ALL chemosensitivity, but also alerting that synthetic lethality by targeting DNA repair system may eventually induce resistant disease due to genetic instability.
Publication Title
FZR1 loss increases sensitivity to DNA damage and consequently promotes murine and human B-cell acute leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 39 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription factor STAT5 plays a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we demonstrate that STAT5 activation cooperates with defects in the pre-BCR signaling components encoded by Blnk, Btk, Prkcb, Nfkb1, and Ikzf1 to initiate B-ALL. STAT5 antagonizes NF-B and IKAROS by opposing regulation of shared target genes. STAT5 binding was enriched at super-enhancers, which were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4, and IKAROS. Patients with high ratios of active STAT5 to NF-B or IKAROS have more aggressive disease. Our studies illustrate that an imbalance of two opposing transcriptional programs drive B-ALL, and suggest that restoring the balance of these pathways may inhibit B-ALL.
Publication Title
Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human B cell lineage acute lymphoblastic leukemia (ALL) cells carrying MLL-AF4 (SEM; BEL) and E2A-PBX1 (697) gene rearrangements were transduced with the mouse ecotropic receptor to permit subsequent entry of retroviral BCR-ABL1 GFP and GFP empty vectors (EV) pseudotyped with murine ecotropic envelope. GFP expression was measured by flow cytometry. Transductions with BCR-ABL1 GFP and GFP empty vectors (EV) were performed in the presence and absence of 2 mmol/l Imatinib (TKI). Washout of Imatinib in one series of experiments is indicated with an arrow. To study gene expression changes in MLL-AF4 and E2A-PBX1 B cell lineage ALL cells that were transduced with empty vectors (EV), BCR-ABL1 GFP in the presence of Imatinib (BCR-ABL1 OFF), washout of Imatinib (BCR-ABL1 ON) and subsequent re-addition of Imatinib, microarray analyses were performed.
Publication Title
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Drosophila melanogaster, Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Study on differential gene expression and splicing between wildtype and clock mutants. This study is part of a comparative analysis of the role of Protein Methyltransferase 5 in the regulation of transcriptional and post-transcriptional processes simultaneously in Arabidopsis and Drosophila.
Publication Title
A methyl transferase links the circadian clock to the regulation of alternative splicing.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Some aspects of the gene expression-based classification method were robust because the gliomasphere cultures retained their classification over many passages, and IDH1 mutant gliomaspheres were all proneural. While gene expression of a subset of gliomasphere cultures was more like the parent tumor than any other tumor, gliomaspheres did not always harbor the same classification as their parent tumor. Classification was not associated with whether a sphere culture was derived from primary or recurrent GBM or associated with the presence of EGFR amplification or rearrangement. Unsupervised clustering of gliomasphere gene expression distinguished 2 general categories (mesenchymal and nonmesenchymal), while multidimensional scaling distinguished 3 main groups and a fourth minor group. Unbiased approaches revealed that PI3Kinase, protein kinase A, mTOR, ERK, Integrin, and beta-catenin pathways were associated with in vitro measures of proliferation and sphere formation. Associating gene expression with gliomasphere phenotypes and patient outcome, we identified genes not previously associated with GBM: PTGR1, which suppresses proliferation, and EFEMP2 and LGALS8, which promote cell proliferation.
Publication Title
Large-scale assessment of the gliomasphere model system.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of the miRNA to a target mRNA, usually in its 3 untranslated region (UTR). As a result, translation of the target mRNA is inhibited and sometimes the mRNA itself can be de-stabilized. The inhibitory effects of miRNAs have been linked to many diverse cellular processes including malignant proliferation and apoptosis, development and differentiation, metabolic processes and neural plasticity. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set.
Publication Title
Detection of a microRNA signal in an in vivo expression set of mRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples