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GSE39671
Homo sapiens
124 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous. Several prognostic factors have been identified that can stratify patients into groups that differ in their relative tendency for disease progression and/or survival. Here, we pursued a subnetwork-based analysis of gene expression profiles to discriminate between groups of patients with disparate risks for CLL progression.
Publication Title
Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 95 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia-cell-expression levels that varied among patients. CLL cells that expressed ZAP-70 or that used unmutated IGHV each had a median expression-level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3 UTRs having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that may enhance B-cell receptor (BCR) signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 levels was a significant independent predictor of longer treatment-free-survival (TFS) or overall survival (OS), whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for OS. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor (BCR), thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.
Publication Title
miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 17 Downloadable Samples
Illumina HiSeq 2000
Description
IGHV mutation status is a well-established prognostic factor in chronic lymphocytic leukemia, and also provides crucial insights into tumor cell biology and function. Currently, determination of IGHV transcript sequence, from which mutation status is calculated, requires a specialized laboratory procedure. RNA sequencing is a method that provides high resolution, high dynamic range transcriptome data that can be used for differential expression, isoform discovery, and variant determination. In this paper, we demonstrate that unselected next-generation RNA sequencing can accurately determine the IGH@ sequence, including the complete sequence of the complementarity-determining region 3 (CDR3), and mutation status of CLL cells, potentially replacing the current method which is a specialized, single-purpose Sanger-sequencing based test. Overall design: CLL cells were sequenced by mRNA-seq on the Illumina platform then subjected to the costom bioinformatic pipeline Ig-ID which yields IGH data
Publication Title
Immunoglobulin transcript sequence and somatic hypermutation computation from unselected RNA-seq reads in chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1492 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 357 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An International Multi-Center Study to Define the Clinical Utility of MicroarrayBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study)
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 204 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An international standardization program towards the application of gene expression profiling in routine leukaemia diagnostics: The MILE study pre-phase.
Publication Title
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina Genome Analyzer
Description
The RNA splicing factor SF3B1 is recurrently mutated in chronic lymphocytic leukemia (CLL), but its functional role in the pathogenesis of this disease has not been firmly established. Here, we show that conditional expression of heterozygous Sf3b1-K700E mutation in mouse B lineage cells disrupts pre-mRNA splicing, alters B-cell development and function, and induces a state of cellular senescence. B-cell restricted expression of this mutation combined with Atm deletion led to the overcoming of cellular senescence, together with enhanced genome instability and the development of clonal B220+CD5+ CLL cells in elderly mice at low penetrance. Mice with CLL-like disease were found to have amplifications of chromosomes 15 and 17. Integrated transcriptome and proteome analysis of the CLL-like cells revealed coordinated dysregulation of multiple CLL-associated cellular processes. This included an unexpected signature of deregulated B-cell receptor (BCR) signaling, which we could also identify in SF3B1-mutated CLL samples from two independent patient cohorts. Notably, human CLLs harboring SF3B1 mutations exhibited greater sensitivity and altered response kinetics to BTK kinase ibrutinib. Our genetically faithful murine model of CLL thus reveals fresh insights regarding the impact of SF3B1 mutation on CLL pathogenesis and suggests a system for identifying vulnerabilities related to this mutation that can be further exploited for the treatment of CLLs with this common mutation. Overall design: RNA-seq of B cells from WT, Sf3b1 MT, Atm MT, DM and DM-CLL mice
Publication Title
A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used the microarrays to obtain the cancerous signatures of T-cell, B-cell, erythroid and megakaryoblastic leukemias in mice.
Publication Title
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43 silenced cells. This was completely restored by co-transfection with HDAC6. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis.
Publication Title
Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The lipocalin Apolipoprotein D (ApoD), known to protect the nervous system against oxidative stress (OS) in model organisms, is up-regulated early in the mouse brain in response to the ROS generator paraquat (PQ). However, the processes triggered by this up-regulation have not been explored.
Publication Title
Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum.
Sample Metadata Fields
Sex, Specimen part
View Samples