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SRP135821
Homo sapiens
9 Downloadable Samples
NextSeq 500
Description
Mutations in the RUNX1 gene (RUNX1mut) have been established in myelodysplasia (MDS), de novo and secondary acute myeloid leukaemia (AML), and are in general associated with an unfavourable clinical outcome. Familial RUNX1 mutations are associated with familial thrombocytopenia and these patients have a predisposition to AML development. However, a number of studies have been performed so far in mice which might be distinct from the human hematopoietic system. Therefore we studied the cellular phenotypes, the RUNX1 binding pattern and expression profile induced by RUNX1mut in cord blood (CB) CD34+ cells and induced pluripotent stem cell (iPSC) and compared these findings to primary RUNX1mut AML's. Overall design: A total of nine samples were subject to RNA-Seq including RUNX1mut-transduced cord blood CD34 cells and time-course iPSCs.
Publication Title
RUNX1 mutations enhance self-renewal and block granulocytic differentiation in human in vitro models and primary AMLs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
RNAi mediated knockdown of BTG1 in the acute lymphoblastic cell line RS4;11 causes this cell line to become resistant to prednisolone treatment when compared to control cells.
Publication Title
BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The Ets transcription factor, ERG, plays a central role in definitive hematopoiesis and its overexpression in acute myeloid leukemia is associated with a stem cell signature and bad prognosis. However, little is known about the underlying mechanism by which ERG causes leukemia. Therefore we sought to identify ERG targets that participate in development of leukemia by integration of expression arrays and Chromatin immunoprecipitation.
Publication Title
Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We performed whole-genome gene expression profiling in Pik3cg-/- mice and subsequent gene ontology clustering of differentially expressed genes compared to wild type mice, in order to investigate the role of Pik3cg in platelet membrane biogenesis and blood coagulation.
Publication Title
Maps of open chromatin guide the functional follow-up of genome-wide association signals: application to hematological traits.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Conventional biochemical and molecular techniques identified previously several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in male adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahr/) with those in mice with wild-type AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 h earlier with 1000 g/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classic AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahr/ mice, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible, were highly induced by TCDD in an AHR-dependent manner. The estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively studied AHR and estrogen receptor pathways. p53 binding sites are over-represented in genes down-regulated by TCDD, suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD.
Publication Title
Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1/, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-, interferon- and NFB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition.
Publication Title
Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations affecting the RAS-MAPK pathway frequently occur in relapse neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis we generated several model systems to define a neuroblastoma RAS-MAPK pathway signature. We could show that activation of this pathway in primary tumors indeed correlates with poor survival and is associated with known activating mutations in ALK and other RAS-MAPK pathway genes. From integrative analysis we could show that mutations in PHOX2B, CIC and DMD are also associated with an activated RAS-MAPK pathway. Mutation of PHOX2B and deletion of CIC in neuroblastoma cell lines induces activation of the RAS-MAPK pathway. This activation was independent of phosphorylated ERK in the CIC knock out systems. Furthermore, deletion of CIC causes a significant increase in tumor growth in vivo. These results show that the RAS-MAPK pathway is involved in tumor progression, and establish CIC as a powerful tumor suppressor that functions downstream of this pathway in neuroblastoma.
Publication Title
RAS-MAPK Pathway-Driven Tumor Progression Is Associated with Loss of CIC and Other Genomic Aberrations in Neuroblastoma.
Sample Metadata Fields
Cell line
View Samples