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Homo sapiens
32 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis of three sets of patient-derived T-ALL xenografted murine lines treated or not treated with Givinostat, to investigate the immediate anti-leukemic effects after 6 hours of in vivo treatment with this histone deacetylase inhibitor.
Publication Title
An immediate transcriptional signature associated with response to the histone deacetylase inhibitor Givinostat in T acute lymphoblastic leukemia xenografts.
Sample Metadata Fields
Specimen part, Treatment
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GSE3920- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
IFNs are highly pleiotropic cytokines also endowed with marked anti-angiogenic activity. In this study, the mRNA expression profiles of endothelial cells (EC) exposed in vitro to IFN-alpha, IFN-beta, or
Publication Title
Identification of genes selectively regulated by IFNs in endothelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although intensification of chemotherapy approaches considerably increased the outcome of pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) patients, a subgroup of them still experience treatment failure and relapse. In this context, we hypothesized that the Nrf2 signalling and its downstream effectors could be involved in sustain therapy resistance in T-ALL, as previously reported in other cancers. Indeed, in this study we identified the Aldo-Keto Reductase (AKR) enzymes AKR1C1-3, as over-expressed in T-ALL samples from therapy-resistant patients, demonstrating their fundamental role in the control of the response to vincristine (VCR) treatment. In particular, we evidence that the modulation of AKR1C1-3 gene expression and activity is sufficient to strongly affect the sensitivity of T-ALL cell lines and primary cells to VCR treatment, but not to daunorubicin, cytarabine or L-asparaginase. Moreover, we found a correlation between the degree of VCR response and the amount of AKR1Cs expression in patient-derived T-ALL xenografts. Interestingly, we show that daunorubicin and cytarabine are able to induce the over-activation of AKR1C enzymes, thus establishing a potential resistance loop generated by the combination of these drugs during T-ALL treatment.
Publication Title
AKR1C enzymes sustain therapy resistance in paediatric T-ALL.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The side population (SP), recently identified in several normal tissues and in a variety of tumors, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer (EOC) and found it in 4 out of 6 primary cultures from xenotransplants, as well as in 9 out of 25 clinical samples analyzed. SP cells from one xenograft bearing a large SP fraction were characterized in detail and they were capable of recreate the full repertoire of cancer cell populations observed in the parent tumor. Moreover, SP cells had higher proliferation rates, were much less apoptotic compared to non-SP cells, and generated tumors more rapidly than non-SP cells.
Publication Title
The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. In this study, we show that ZNF521 is significantly upregulated in MLL translocated AML patients from a large pediatric cohort, regardless of the type of MLL translocations such as MLL-AF9, MLL-ENL, MLL-AF10 and MLL-AF6 fusion genes. Our in vitro functional studies demonstrate that ZNF521 play a critical role in the maintenance of the undifferentiated state of MLL-rearranged cells. Furthermore, analysis of the ZNF521 gene promoter region shows that ZNF521 is a direct downstream target of both MLL-AF9 and MLL-ENL fusion proteins. Gene expression profiling of MLL-AF9-rearranged THP-1 cells after depletion of ZNF521 reveals correlation with several expression signatures including stem cell-like and MLL fusion dependent programs. These data suggest that MLL fusion proteins activate ZNF521 expression to maintain the undifferentiated state and contribute to leukemogenesis.
Publication Title
ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Comparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of MSI2 in vivo
Publication Title
Transformation of the intestinal epithelium by the MSI2 RNA-binding protein.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Genetic and epigenetic alterations cause a dysregulated developmental program in leukemia. The MSI2 RNA binding protein has been previously shown to predict poor survival in leukemia. We demonstrate that the conditional deletion of Msi2 results in delayed leukemogenesis, reduced disease burden and a loss of LSC function. Gene expression profiling of the Msi2 ablated LSCs demonstrates a loss of the HSC/LSC and an increase in the differentiation program. The gene signature from the Msi2 deleted LSCs correlates with survival in AML patients. MSI2’s maintains the MLL self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc and Ikzf2. We further demonstrate that shRNA depletion of the MLL target gene Ikzf2 also contributes to MLL leukemia cell survival. Our data provides evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and a rationale for clinically targeting MSI2 in myeloid leukemia. Overall design: RNA-Seq was performed on sorted c-Kit high leukemic cells from 2 Msi2 -/- and 2 Msi2 f/f mice.
Publication Title
Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle.
Publication Title
Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood.
Publication Title
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1 down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1 on expression of genes encoding secreted proteins. Interestingly, PGC-1 requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1 modulates the secretome of mouse embryonic fibroblasts (MEFs).
Publication Title
Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part
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