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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- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A distinct type of macrophages helps breast cancer cells to overcome rate-limiting steps in the metastatic process and establish lethal metastatic tumors. Since only a minor population of cancer cells can establish macroscopic metastatic tumors, we hypothesized that this metastatic cancer cell population have higher expression of receptors for macrophage-derived ligands compared to their parental cells.
Publication Title
Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.
Sample Metadata Fields
Specimen part
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- Homo sapiens
- 57 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Popular methods for library preparation in RNA-seq such as Illumina TruSeq® RNA v2 kit use a poly-A pulldown strategy. Such methods can cause loss of coverage at the 5’ end of genes, impacting the ability to detect fusions when used on degraded samples. The goal of this study was to quantify the effects RNA degradation has on fusion detection when using poly-A selected mRNA and to identify the variables involved in this process Methods: Total RNA was extracted from solid tumor tissue and whole blood using the Qiagen® miRNeasy Micro and Mini kits, respectively. The KU812 cell line was purchased from Sigma-Aldrich (St. Louis, MO) and UHR (Universal Human Reference RNA) was purchased from Agilent (Santa Clara, CA). UHR is a mixture of cell lines derived from breast adenocarcinoma, hepatoblastoma, cervix adenocarcinoma, testis embryonal carcinoma, gliobastoma, melanoma, liposarcoma, histiocytic lymphoma, lymphoblastic leukemia and plasmocytoma. For Degradation experiments, two micrograms of human universal reference RNA (UHR) (Agilent Technologies, Santa Clara, CA) and 1ug of RNA extracted from KU812 cell line (purchased from ATCC) were degraded at 74oC from 1 to 11 minutes in 1 minute intervals, using the NEBNext® Magnesium RNA Fragmentation Module Kit (NEB, Ipswich, MA). RNA was then purified and concentrated with RNeasy MinElute Cleanup Kit (Qiagen, Valencia, CA). Results: In this study, we designed experiments using artificially degraded RNA from cell lines as well as naturally degraded RNA from tissue samples to quantify the effect RNA degradation has on fusion detection when using poly-A selected RNA libraries We found that both the RNA degradation level and the distance from the 3’ end of a gene, negatively impact the read coverage profile in RNA-seq. Furthermore, the median transcript coverage decreases exponentially as a function of the distance from the 3’ end and there is a linear relationship between the coverage decay rate and the RNA integrity number (RIN). Conclusions: we found that when using poly-A pulldown techniques for library preparation in RNA-seq, the fusion sensitivity is negatively impacted by both sample degradation and distance of the fusion breakpoint from the 3’ end and developed graphs that show such effect. Such graphs can be useful in assessing the fusion sensitivity of RNA-seq in both research and clinical settings Overall design: Sequencing data was generated using Hiseq 2500 with a library of 101 paired end reads in the rapid run mode
Publication Title
Impact of RNA degradation on fusion detection by RNA-seq.
Sample Metadata Fields
Disease, Subject
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
- 53 Downloadable Samples
- Illumina HiSeq 2500
Description
The meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.
Publication Title
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples