Gene expression profiles of monocytes derived from chronic lymphocytic leukemia patients and normal controls
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE35179 | GEO | 2013/01/10
SECONDARY ACCESSION(S): PRJNA150665
REPOSITORIES: GEO
Similar Datasets
Project description:We collected monocytes from peripheral blood of 5 chronic lymphocytic leukemia (CLL) patients and 5 healthy donors and we performed gene expression analysis by microarray. Comparison of gene expression profiles (GEPs) between CLL-derived and normal monocytes was used to discover molecular abnormalities in this nonmalignant immune cellular population in leukemia-bearing patients. Although analysed cells were not part of the malignant clone, in unsupervised hierarchical clustering analysis, GEPs of normal monocytes were clearly distinguishable from those of monocytes obtained from CLL patients. Supervised analysis identified 65 genes significantly up-regulated and 48 genes down-regulated in CLL monocytes compared with monocytes from normal controls (FC=2, p<0.05). Modification of gene expression profile would imply impairment of phagocytosis and production of immunosuppressive mediators in CLL-derived monocytes. The alterations described in our study further contribute to characterize the complexity of factors potentially involved in acquired immune deficiency of CLL patients. Large-scale gene expression profiling (GEP) was performed on total RNA extracted from purified CD14+ monocytes (RNeasy Mini kit Plus, QIAGEN, Valencia, CA, USA) isolated from 5 individual CLL patients and 5 healthy controls by hybridization on 4X44K Whole Human Genome Microarray (Agilent Technologies, Palo alto, CA). Fluorescence data were analysed with Feature Extraction Software v.10.5 (Agilent Technologies) an QC Chart tool v.1.3. Agglomerative two-dimensional clustering analysis and supervised analyses based on t-test were performed using Gene Spring GX (Agilent) software. Genes were defined as differentially expressed between groups at a significant level of p<0.05 and with a fold change cut off ± 2 in all the pair wise comparisons.
2013-01-10 | E-GEOD-35179 | biostudies-arrayexpress
Project description:B cell chronic lymphocytic leukemia - A model with immune response
Seema Nanda 1, , Lisette dePillis 2, and Ami Radunskaya 3,
1.
Tata Institute of Fundamental Research, Centre for Applicable Mathematics, Bangalore 560065, India
2.
Department of Mathematics, Harvey Mudd College, Claremont, CA 91711
3.
Department of Mathematics, Pomona College, Claremont, CA, 91711, United States
Abstract
B cell chronic lymphocytic leukemia (B-CLL) is known to have substantial clinical heterogeneity. There is no cure, but treatments allow for disease management. However, the wide range of clinical courses experienced by B-CLL patients makes prognosis and hence treatment a significant challenge. In an attempt to study disease progression across different patients via a unified yet flexible approach, we present a mathematical model of B-CLL with immune response, that can capture both rapid and slow disease progression. This model includes four different cell populations in the peripheral blood of humans: B-CLL cells, NK cells, cytotoxic T cells and helper T cells. We analyze existing data in the medical literature, determine ranges of values for parameters of the model, and compare our model outcomes to clinical patient data. The goal of this work is to provide a tool that may shed light on factors affecting the course of disease progression in patients. This modeling tool can serve as a foundation upon which future treatments can be based.
Keywords: NK cell, chronic lymphocytic leukemia, mathematical model, T cell., B-CLL.
2020-01-09 | MODEL2001090002 | BioModels
Project 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. Purified T-cells of B-CLL patients and normal donor T-cells were analyzed on microarrays to identify differentially expressed genes. The normal donor T-cell control data sets (n=8) have been previously published in the GDS2908 record.
2009-11-25 | E-GEOD-19147 | biostudies-arrayexpress
Project description:Analysis of the expression profile of 290 mRNA's, measured with the nCounter (Nanostring Technologies platform), in 30 samples from the peripheral blood of CLL patients Chronic lymphocytic leukemia (CLL) is a clonal malignancy of mature B cells that displays a great clinical heterogeneity, with many patients having an indolent disease that will not require intervention for many years, while others present an aggressive and symptomatic leukemia requiring immediate treatment. Although there is no cure for CLL, the disease is treatable and current standard chemotherapy regimens have been shown to prolong survival. Recent advances in our understanding of the biology of CLL have led to the identification of numerous cellular and molecular markers with potential diagnostic, prognostic and therapeutic significance. We have used the recently developed digital multiplexed gene-expression technique (DMGE) to analyze a cohort of 30 CLL patients for the presence of specific genes with known diagnostic and prognostic potential. Starting from a set of 290 genes we were able to develop a molecular signature, based on the analysis of 13 genes, which allows distinguishing unambiguously CLL from normal peripheral blood and from normal B cells, and a second signature based on 24 genes, which distinguishes mutated from unmutated cases (LymphCLL Mut). A third classifier (LymphCLL Diag), based on a 44-gene signature, distinguished CLL cases from a series of other B-cell chronic lymphoproliferative disorders (n=51). This analysis is easy to perform, ideal for clinical trials and normal routine diagnosis even in small hospitals.
2015-04-30 | GSE66425 | GEO
Project description:Chronic lymphocytic leukemia (CLL) is a common and heterogeneous disease. An accurate prediction of outcome is highly relevant for the development of personalized treatment strategies. Microarray technology was shown to be a useful tool for the development of prognostic gene expression scores. However, there are no gene expression scores which are able to predict overall survival in CLL based on the expression of few genes that are better than established prognostic markers. We correlated 151 CLL microarray data sets with overall survival using Cox regression and supervised principal component analysis to derive a prognostic score. This score based on the expression levels of eight genes and was validated in an independent group of 149 CLL patients by quantitative real time PCR. The score was predictive for overall survival and time to treatment in univariate Cox regression in the validation data set (both: p<0.001) and in a multivariate analysis after adjustment for 17p and 11q deletions and the IgVH-status. The score achieved superior prognostic accuracy compared to models based on genomic aberrations and IgVH-status and may support personalized therapy. Analysis of 151 samples of peripheral blood mononuclear cells (107 HGU-133plus2; 44 HGU-133A; 44 HGU-133B) from adult patients with chronic lymphocytic leukemia (CLL)
2011-10-13 | E-GEOD-22762 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is still incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. In order to get more detailed insights into CLL development, we performed a comprehensive proteome analysis of primary human CLL cells and B cells from young and age-matched healthy individuals. For comparison, we also analyzed the chronic B cell leukemia cell line JVM-13 showing rather limited similarity to the primary cells. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and CLL patients. Remarkably, B cells from aged controls displayed significant regulation of proteins related to metabolic processes and stress response in mitochondria such as DLAT, FIS1 and NDUFAB1 as well as DNA repair including RAD9A, MGMT and XPA. Interestingly, these alterations apparently correlating with aging of B cells may also be essential for tumorigenesis and were observed similarly in CLL cells. In CLL cells, in addition, some remarkable unique features like the loss of tumor suppressor molecules PNN and JARID2, and high expression of CCDC88A, PIGR and ID3 otherwise associated with epithelial mesenchymal transition and stemness were determined. Furthermore, while typical hallmarks of cancer such as cell proliferation were hardly apparent for CLL cells, alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify previously unrecognized features of CLL cells and suggest that aging may be accompanied by proteome alterations functionally relevant for predisposing B cells to transform to CLL cells.
| MSV000082941 | MassIVE
Project 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.
2009-11-25 | GSE19147 | GEO
Project description:MIR15A and MIR16-1, located in chromosomal band 13q14, are tumor suppressor miRNAs often deleted and downregulated in chronic lymphocytic leukemia (CLL). This downregulation is not only due to loss of 13q, as it occurs also in 13q+/+ CLL patients. We found that a subgroup of CLL patients has a dysregulation of miR-15 /-16 processing intermediates due to defective processing by Drosha. These patients have reduced levels of miR-15a, miR-16 and miR-15b (another member of the miR-15 family), but not of most other miRNAs. Thus, we show that modulation of miRNA maturation leads to specific downregulation of a family of tumor suppressor miRNAs in leukemic cells. 11 normal processing CLL sample; 12 processing defective CLL patients
2011-12-31 | E-GEOD-30927 | biostudies-arrayexpress
Project description:B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course that reflects its heterogeneous genomic pattern. To better define molecular subtypes of the disease, we performed SNP and gene expression profiling microarray analyses in a panel of early stage (Binet A) patients. A clustering analysis of genomic profiles identified four significant groups mainly driven by del(13)(q14) and trisomy 12. Notably, patients with del(13)(q14) were grouped in two separate clusters based on the presence of a biallelic loss and the extension of the deletion. The shorter monoallelic deleted 13q14 region was found to be 635 kb in length, not encompassing the mir-15a/16-1 locus. Interestingly, the mir-15a and mir-16 expression was found to be significantly down-regulated only in patients with biallelic loss. Furthermore, a multiclass supervised analysis identified a different transcriptional signatures in the two genomic subgroups with del(13)(q14). Finally, an integrative approach identified 93 transcripts, mainly mapped to chromosome 12 and 13q12-q14.3, whose expression was significantly correlated with the DNA copy number. Overall, our data further support the notion that transcription deregulation in B-CLL could be mostly due to a gene dosage effect and underscore the presence of two distinct molecular types of 13q14 deleted patients with potential clinical relevance. Transcriptional analysis of 60 B-CLL patients, and genotyping analysis of 100 B-CLL patients, in early stage disease (Binet A). This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 60 newly diagnosed patients (Binet stage A). Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 3 micrograms of total RNA was processed and, in accordance with the manufacturer's protocols, 15 micrograms of fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133A Arrays (Affymetrix Inc.). The arrays were scanned using the GeneChip Scanner 3000 7G. The images were acquired using Affymetrix GeneChip Operating Software (GCOS version 1.4) and the probe level data converted to expression values using the Bioconductor function for the Robust Multi-Array average (RMA) procedure (Irizarry et al, 2003), in which perfect match intensities are background adjusted and quantile-quantile normalised. This series of microarray experiments contains the genome-wide profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 100 newly diagnosed patients (Binet stage A). Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple-positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 250 nanograms of genomic DNA was processed and, in accordance with the manufacturer's protocols, 90 micrograms of fragmented biotin-labeled DNA were hybridized on GeneChip Human Mapping 250K NspI Arrays (Affymetrix Inc.). The arrays were scanned using the GeneChip Scanner 3000 7G. The images were acquired using Affymetrix GeneChip Operating Software (GCOS version 1.4). The raw data for individual SNPs were extracted from CEL files and converted into signal intensities using GTYPE 4.1 and Affymetrix Copy Number Analysis Tool (CNAT 4.0.1) softwares using the Hidden Markov Model algorithm with a genomic smoothing window set to 0. After the pre-processing, piecewise constant estimates of the underlying local DNA copy number (CN) variation was calculated using the DNAcopy Bioconductor package, which looks for optimal breakpoints using circular binary segmentation (CBS).
2010-09-01 | E-GEOD-16746 | biostudies-arrayexpress
Project description:[original title] LMP-420: a novel purine nucleoside analogue with potent cytotoxic effects for chronic lymphocytic leukemia cells and minimal toxicity for normal hematopoietic cells. LMP-420 induces cytotoxicity and apoptosis to CLL cells in vitro without any negative effects to normal immune cells. This gene expression experiment compares CLL cells treated with LMP-420 versus media alone to investigate the mechanism of action of LMP-420. CLL cells from 13 patients were treated with LMP-420 or media for 24 hours, then RNA was extracted and assayed on U133Plus2 GeneChips.
2011-02-01 | E-GEOD-20211 | biostudies-arrayexpress