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GSE13425
Homo sapiens
190 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Childhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
Publication Title
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Childhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
Publication Title
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T-cell acute lymphoblastic leukemia (T-ALL) is mostly characterized by specific chromosomal abnormalities, some occurring in a mutually exclusive manner possibly delineating specific T-ALL subgroups. One subgroup, including MLL-rearranged, CALM-AF10 or inv(7)(p15q34) cases, is characterized by elevated expression of HOXA genes. Using a gene expression based clustering analysis of 67 T-ALL cases with recurrent molecular genetic abnormalities and 25 samples lacking apparent aberrations, we identified 5 new cases with elevated HOXA levels. Using array-CGH, a cryptic and recurrent deletion, del(9)(q34.11q34.13), was exclusively identified in 3 of these 5 cases. This deletion results in a conserved SET-NUP214 fusion product, that was also identified in the T-ALL cell line LOUCY. SET-NUP214 binds in the promoter regions of specific HOXA genes, where it may interact with CRM1 and DOT1L leading to the transcriptional activation of HOXA genes. Targeted inhibition of SET-NUP214 by siRNA abolished expression of HOXA genes, inhibited proliferation and induced differentiation in LOUCY but not in other T-ALL lines. We conclude that SET-NUP214 may contribute to the pathogenesis of T-ALL by enforcing T-cell differentiation arrest.
Publication Title
The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 315 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to identify relevant, molecularly defined subgroups in Multiple Myeloma (MM), gene expression profiling (GEP) was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/ GMMG-HD4 trial using Affymetrix GeneChip U133 plus 2.0 arrays. Hierarchical clustering identified 10 distinct subgroups. Using this dataset as training data, a prognostic signature was built. The dataset consists of 282 CEL files previously used in the hierarchical clustering study of Broyl et al (Blood, 116(14):2543-53, 2010) outlined above. To this set 8 CEL-files/gene expression profiles were added. Using this set of 290 CEL-files, a prognostic signature of 92 genes (EMC-92-genesignature) was generated by supervised principal components analysis combined with simulated annealing (Kuiper et al.).
Publication Title
Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 116 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify novel oncogenic pathways in T-cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lacked rearrangements of known oncogenes. One subtype associated with cortical arrest, expression of cell cycle genes and ectopic NKX2-1 or NKX2-2 expression for which rearrangements were identified. The second subtype associated with immature T-cell development and high expression of the MEF2C transcription factor as consequence of rearrangements of MEF2C, transcription factors that target MEF2C or MEF2C-associated cofactors. We propose NKX2-1, NKX2-2 and MEF2C as T-ALL oncogenes that are activated by various rearrangements.
Publication Title
Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease caused by an alanine tract expansion mutation in Poly(A)-binding protein nuclear 1 (expPABPN1). To model OPMD in a myogenic and physiological context, we generated mouse myoblast cell clones stably expressing either human wild type (WT) or expPABPN1 at low levels. The transgene expression is induced upon myotube differentiation and results in formation of insoluble nuclear PABPN1 aggregates that are similar to the in vivo aggregates. Quantitative analysis of PABPN1 protein in myotube cultures revealed that expPABPN1 accumulation and aggregation is greater than that of the WT protein. In a comparative study we found that aggregation of expPABPN1 is more affected by inhibition of proteasome activity, as compared with the WT PABPN1 aggregation. Consistent with this, in myotubes cultures expressing expPABPN1 deregulation of the proteasome was identified as the most significantly deregulated pathway. Differences in the accumulation of soluble WT and expPABPN1 were consistent with differences in ubiquitination and protein turnover. This study indicates, for the first time, that in myotubes the ratio of soluble to insoluble expPABPN1 is significantly lower compared to that of the WT protein. We suggest that this difference can contribute to muscle weakness in OPMD.
Publication Title
Modeling oculopharyngeal muscular dystrophy in myotube cultures reveals reduced accumulation of soluble mutant PABPN1 protein.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We address the function of HEXIM, an inhibitor of the general transcriptional elongation regulator P-TEFb which regulates the transcriptional status of many developmental genes, during Drosophila development. We showed that HEXIM knockdown mutants display organs development failure. In the wing disc, it induces apoptosis and affects Hh signaling. The continuous death of proliferative cells is compensated by apoptosis-induced cell proliferation, in a manner similar to that of differentiated cells, together with high levels of Hh and Ci. We completed this analysis with microarrays to characterize the molecular phenotype of HEXIM knockdown during eye differentiation.
Publication Title
Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 30 Downloadable Samples
Illumina HiSeq 2000
Description
HIV-1 nucleoside reverse transcriptase inhibitor (NRTI) use is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to NRTIs has predominantly been assigned to mitochondrial polymerase-? inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of these drugs, which are rarely discussed in the literature, include direct inhibition of the mitochondrial respiratory chain (MRC), decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC), which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure. Overall design: RNA-seq on Caenorhabditis elegans exposed to DMSO, 3''-azido-3''-deoxythymidine (zidovudine or AZT), 2'',3''-didehydro-2'',3''-deoxythymidine (stavudine or d4T), 3''-deoxy-3''-fluorothymidine (alovudine or FLT) or untreated control after 24 or 72 hours of exposure.
Publication Title
Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- NextSeq 500
Description
EMT, Epithelial to mesenchymal transition is a developmental biology process associated with migration, known to be involved in cancer metastasis. To study this process, we used the breast epithelial cell line MCF10A that enter in EMT after treatment with the cytokine TGFB or by expression of EMT transcriptor factor SNAIL. Overall design: mRNA profiles of MCF10A cells treated for 1 or 6 days with TGFb (done in duplicate), and mRNA profiles of Snail inducible line, MCF10A-SNAIl, induced for 1 or 6 days.
Publication Title
Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
Cell line, Subject
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used Affymetrix Arabidopsis ATH1 GeneChip to profile RNAs active in wild type columbia (glabrous) and CaMV::DME pollen and stamens.
Publication Title
Identification of putative Arabidopsis DEMETER target genes by GeneChip analysis.
Sample Metadata Fields
No sample metadata fields
View Samples