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GSE42204
Homo sapiens
63 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The multifunctional protein lipopolysaccharide-induced TNFalpha factor (LITAF) induces the secretion of inflammatory cytokines in monocytes and regulates protein degradation in neural cells. In B-cell lymphomas, LITAF is frequently inactivated by epigenetic mechanisms, but beyond these data little is known about its regulation and function. Immunohistochemical and gene expression profiling analyses of normal and malignant B-cells revealed that LITAF and BCL6 exhibited opposite expression patterns. Accordingly, chromatin immunoprecipitation and luciferase experiments showed that LITAF is transcriptionally repressed by BCL6 in germinal center (GC) lymphocytes and in B-cell lymphoma cells. Gain- and-loss-of-function assays demonstrated that LITAF does not exert any of its previous roles. Conversely, LITAF co-localized with autophagosomes in B-cells whereby activated autophagic responses, which were abrogated upon LITAF silencing. Therefore, BCL6-mediated transcriptional repression of LITAF may contribute to an appropriate GC reaction by suppressing autophagy in GC lymphocytes, whereas constitutive repression of autophagic responses may promote B-cell lymphoma development.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The multifunctional protein lipopolysaccharide-induced TNFalpha factor (LITAF) induces the secretion of inflammatory cytokines in monocytes and regulates protein degradation in neural cells. In B-cell lymphomas, LITAF is frequently inactivated by epigenetic mechanisms, but beyond these data little is known about its regulation and function. Immunohistochemical and gene expression profiling analyses of normal and malignant B-cells revealed that LITAF and BCL6 exhibited opposite expression patterns. Accordingly, chromatin immunoprecipitation and luciferase experiments showed that LITAF is transcriptionally repressed by BCL6 in germinal center (GC) lymphocytes and in B-cell lymphoma cells. Gain- and-loss-of-function assays demonstrated that LITAF does not exert any of its previous roles. Conversely, LITAF co-localized with autophagosomes in B-cells whereby activated autophagic responses, which were abrogated upon LITAF silencing. Therefore, BCL6-mediated transcriptional repression of LITAF may contribute to an appropriate GC reaction by suppressing autophagy in GC lymphocytes, whereas constitutive repression of autophagic responses may promote B-cell lymphoma development.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Brain tumor neurospheres (BTCSs) are cancer cells with neural stem cell-like properties found in the fatal brain tumor glioblastoma multiforme (GBM). These cells account for less than 1% of total tumor cells, are poorly differentiated and are believed to be involved in tumor induction, progression, treatment resistance and relapse. Specific miRNAs play important roles in modulating the proliferation and differentiation of neural stem cells, therefore, we aimed to identify miRNAs controlling differentiation in GBM-BTSCs through high throughput screening miRNA array profiling. We compared the miRNA expression profiles at the neurosphere state and upon 4 and 14days of differentiation by using LIMMA, finding 21 differentially expressed miRNAs : hsa-miR-103, hsa-miR-106a, hsa-miR-106b, hsa-miR-15b, hsa-miR-17, hsa-miR-19a, hsa-miR-20a, hsa-miR-25, hsa-miR-301a and hsa-miR-93 were found up-regulated upon differentiation, while hsa-miR-100, hsa-miR-1259, hsa-miR-21, hsa-miR-22, hsa-miR-221, hsa-miR-222, hsa-miR-23b, hsa-miR-27a, hsa-miR-27b, hsa-miR-29a and hsa-miR-29b were down-regulated. Expression of 11 of the 21 miRNAs was examined by qPCR and 7 of them were validated: hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222 increased their expression upon differentiation, while hsa-miR-93 and hsa-miR-106a were inhibited. Functional studies demonstrated that miR-21 over-expression induced the expression of glial and/or neuronal cell markers in the neurospheres, possibly due to SPRY1 targeting by miR-21 in these cells, while miR-221 and miR-222 inhibition at the differentiated state reduced the expression of those differentiation markers. On the other hand, miR-29a and miR-29b targeted MCL1 in the GBM neurospheres and increased apoptotic cell death.
Publication Title
Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The cellular origin and malignant transformation of Waldenström macroglobulinemia.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Although information on the molecular pathogenesis of Waldenstrms Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenstrms clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenstrms clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenstrms clone.
Publication Title
The cellular origin and malignant transformation of Waldenström macroglobulinemia.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) relates to inferior survival in multiple myeloma (MM). MRD PCs are therefore a minor clone able to recapitulate the initial tumor burden at relapse and accordingly, its characterization may represent a unique model to understand chemoresistance; unfortunately, the MRD clone has never been biologically investigated. Here, we compared the antigenic profile of MRD vs. diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study, and showed that the MRD clone is enriched by cells over-expressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4) and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs. diagnostic PCs showed identical copy number alterations (CNAs) in 3/8 cases, 2 patients with linear acquisition of additional CNAs in MRD clonal PCs, and 3 cases with variable acquisition and loss of CNAs over time. The MRD clone showed significant downregulation of genes particularly related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and identifies chemoresistant PCs in vitro. Together, we show that therapy-induced clonal selection is already present at the MRD stage, in which chemoresistant PCs show a specific phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles.
Publication Title
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Sample Metadata Fields
Specimen part, Disease
View Samples