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GSE13273
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To analyze the functional relevance of LSD1 in neuroblastic tumors, SH-SY5Y cells were transiently transfected with siRNA directed against LSD1 or with a scrambled control siRNA. Microarray analysis revealed changes in expression that were consistent with these observations 72 hours after LSD1 knock-down. At this time, 28 genes were significantly induced at least 1.5-fold and 29 genes were significantly repressed at least 1.5-fold. Among the 28 induced genes, 4 are markers of cytoskeletal remodelling (TNS1, TPM1, DNM2, DNAL4), indicating differentiation, and 3 (TPM1, DNM2 and SHANK2) are functionally linked to neurite dynamics and synaptic trafficking. TaqMan quantitative RT-PCR confirmed the expression changes detected via microarray analysis for LSD1, DNAL4, DNM2, TNS1 and TPM1
Publication Title
Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 148 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 148 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The pathogenesis of diffuse large B cell lymphomas (DLBCL) is only partly understood. We analyzed 148 DLBCL by high resolution single nucleotide polymorphism (SNP)-chips to characterize genomic imbalances. Seventy-nine cases were of the germinal center B-cell like (GCB) type of DLBCL, 49 of the activated B-cell like (ABC) subtype and 20 were type 3 DLBCL. Twenty-four regions of recurrent genomic gains and 38 regions of recurrent genomic losses were identified over the whole cohort, with a median of 25 imbalances per case for ABC-DLBCL and 19 per case for GCB-DLBCL. Several recurrent copy number changes showed differential frequencies in the GCB- and ABC-DLBCL subgroups, including gains of HDAC7A predominantly in GCB-DLBCL (38% of cases) and losses of BACH2 and CASP8AP2 predominantly in ABC-DLBCL (35%), hinting at disparate pathogenetic mechanisms in these entities. Correlating gene expression and copy number revealed a strong gene dosage effect in all tumors, with 34% of probesets showing a concordant expression change in affected regions. Two new potential tumor suppressor genes emerging from the analysis, CASP3 and IL5RA, were sequenced in 10 and 16 candidate cases, respectively. However, no mutations were found, pointing to a potential haploinsufficiency effect of these genes, considering their reduced expression in cases with deletions. This work thus describes differences and similarities in the landscape of genomic aberrations in the DLBCL subgroups in a large collection of cases, confirming already known targets, but also discovering novel copy number changes with possible pathogenetic relevance.
Publication Title
Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol.
Publication Title
Smac mimetic LBW242 sensitizes XIAP-overexpressing neuroblastoma cells for TNF-α-independent apoptosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The cellular origin of chronic lymphocytic leukemia (CLL) is debated. Transcriptome analysis of CLL and normal peripheral blood and splenic B cell subsets displayed highest similarity of CLL to mature CD5+ B cells. We identified a distinct CD5+CD27+ post-germinal center B cell subset, and revealed that immunoglobulin V gene mutated CLL are more similar to mutated CD5+ B cells, whereas unmutated CLL are more related to unmutated CD5+ B cells. Stereotyped immunoglobulin V gene rearrangements were significantly enriched among CD5+ B cells, providing further genetic evidence for a derivation of CLL from CD5+ B cells. Moreover, we identified deregulated expression patterns providing novel insights into the pathophysiology of CLL, including downregulation of EBF1 and KLF family members.
Publication Title
Cellular origin and pathophysiology of chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Analysis of T-cells isolated from CD3+ T-cells of patients with B-cell chronic lymphocytic leukemia (B-CLL). In contrast to other types of cancers, the non-malignant T-cell compartment of B CLL patients is expanded. Results provide insights into the role of T-cells in B-CLL.
Publication Title
Expanded CD8+ T cells of murine and human CLL are driven into a senescent KLRG1+ effector memory phenotype.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these sub-haploinsufficient cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Neurotrophin receptors play a pivotal role in the biology and prognosis of neuroblastoma (NB). While expression of TrkA/NTRK1 confers a good prognosis to NB patients, expression of TrkB/NTRK2 is associated with unfavorable outcome. We have transfected the neurotrophin-receptor null cell line SY5Y with either full-length TrkA or TrkB and performed transcriptional profiling to analyse the effects of Trk-expression without activation and in a time course after activation.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Bone marrow fibrosis (BMF) is a rare complication in acute leukemia. In pediatrics, it predominantly occurs in acute megakaryoblastic leukemia (AMKL) and here especially in patients with trisomy 21, called myeloid leukemia in Down syndrome (ML-DS). Defects in mesenchymal stromal cells (MSCs) and cytokines specifically released by the myeloid blasts are the main drivers of fibrosis in the bone marrow niche (BMN). In order to determine which factors are necessary/sufficient for the BMF, we first established MSCs from pediatric patients with AMKL and ML-DS. Healthy donor (HD) control MSCs were established from children and adolescents ≤18 years of age. Steady-state analyses of the MSCs revealed that patient-derived MSCs exhibited decreased adipogenic differentiation potential, enrichment of proliferation-associated genes and upregulation of the oncofetal protein IF2B3. TGFB1 exposure in vitro promoted early profibrotic changes in all three MSC entities. To study BMF induction for longer periods of time, we created an in vivo humanized artificial BMN in immunodeficient mice. Injection of AMKL blasts as producers of TGFB1 specifically induced fibrosis grade I/II in a dose-dependent fashion, thus strongly suggesting TGFB1 excess to be sufficient for BMF. Our in vivo BMF model will be instrumental to specifically prevent the BMF and to identify potentially druggable target genes.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples