Homo sapiens
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PROVIDER: PRJNA283501 | ENA |
REPOSITORIES: ENA
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Project description:In chronic lymphocytic leukemia (CLL) the increment in peripheral blood lymphocytes is slower than the expected increment calculated from the cells’ proliferation rate, suggesting that cellular proliferation and apoptosis are concurrent. Exploring this phenomenon, we found overexpression of caspase3, higher cleaved poly (ADP-ribose) polymerase (PARP) levels (P <0.007), and a higher apoptosis rate in cells from patients with high counts compared with cells from patients with low counts. Although we previously found that signal transducer and activator of transcription 3 (STAT3) protects CLL cells from apoptosis, STAT3 levels were significantly higher in cells from patients with high counts than in cells from patients with low counts. Furthermore, overexpression of STAT3 in MM-1 cells did not protect the cells. Rather, it upregulated caspase3 and induced apoptosis. Remarkably, putative STAT3 binding sites were identified in the caspase3 promoter and a luciferase assay, chromatin immunoprecipitation (ChIP), and an electromobility shift assay (EMSA) revealed that STAT3 activated caspase3. However, caspase3 levels increased only when STAT3 levels were sufficiently high. Using ChIP and EMSA, we found that STAT3 binds with low affinity to the caspase3 promoter, suggesting that at high levels, STAT3 activates a negative proapoptotic feedback mechanism. 4 samples from patients with high-count CLL were compared to 4 samples from patients with low-count CLL
2015-05-12 | E-GEOD-68721 | biostudies-arrayexpress
Project description:In chronic lymphocytic leukemia (CLL) the increment in peripheral blood lymphocytes is slower than the expected increment calculated from the cells’ proliferation rate, suggesting that cellular proliferation and apoptosis are concurrent. Exploring this phenomenon, we found overexpression of caspase3, higher cleaved poly (ADP-ribose) polymerase (PARP) levels (P <0.007), and a higher apoptosis rate in cells from patients with high counts compared with cells from patients with low counts. Although we previously found that signal transducer and activator of transcription 3 (STAT3) protects CLL cells from apoptosis, STAT3 levels were significantly higher in cells from patients with high counts than in cells from patients with low counts. Furthermore, overexpression of STAT3 in MM-1 cells did not protect the cells. Rather, it upregulated caspase3 and induced apoptosis. Remarkably, putative STAT3 binding sites were identified in the caspase3 promoter and a luciferase assay, chromatin immunoprecipitation (ChIP), and an electromobility shift assay (EMSA) revealed that STAT3 activated caspase3. However, caspase3 levels increased only when STAT3 levels were sufficiently high. Using ChIP and EMSA, we found that STAT3 binds with low affinity to the caspase3 promoter, suggesting that at high levels, STAT3 activates a negative proapoptotic feedback mechanism.
2015-05-12 | GSE68721 | GEO
Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Keywords: comparison of poor and good prognosis CLL patient transcriptome regarding ZAP70 expression
2009-04-18 | GSE12734 | GEO
Project description:Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL), but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Experiment Overall Design: Two groups of seven CLL patients were compared, selected on the basis of either high or low ZAP70 mRNA expression. Total RNA from CD19+ purified cells was exctracted and hybidyzed on Affymetrix GeneChipî Human Genome U133 Plus 2.0 Array. Amplification, hybridization and scanning were done according to standard Affymetrix protocols (www.affymetrix.com). CEL files were ,normalized with RMA method.
2009-04-25 | E-GEOD-12734 | 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:In the present study, the methylation profiling (MeDIP) was carried out in 14 treatment-naive, early stage (Rai stage 0-2) CLL patients and pooled 19+ normal controls. To find an association of methylation with IGHV mutation status, CLL patients were further segregated into IGHV unmutated (n=9) and IGHV mutated (n=5) subgroups. The methylation signature obtained for CLL versus nornal controls and; unmutated versus mutated CLL was integrated with gene expression profile of these patients and the results were correlated with clinical outcome.
2017-05-29 | GSE81936 | GEO
Project description:It has been widely recognized that a 13q14 deletion is often found in CLL and that this deletion is associated with a good prognosis. Such deletions are sometime detected only by fluorescence in situ hybridization (FISH) [1] because they are too small to be detected by banding. We report here a small deletion that is undetectable by FISH but identifiable by high-resolution comparative genomic hybridization (CGH) arrays. A 62-year-old patient with previously untreated chronic lymphocytic leukemia (CLL; BinetÕs stage A) was studied because of a recent increase of his lymphocyte counts. The patient had been in stage A since the initial diagnosis was made 12 years before. At the time of cytogenetic analysis, the peripheral lymphocyte count was 65.3 g/L with weak llight chain surface imunoglobulin expression and a Matutes score of 5/5. The karyotype of 12-O-tetradecanoylphorbal 13-acetate-stimulated blood cells was 46,X,-Y[3]/46,XY [17]. FISH with X and Y probes confirmed that 90% of the blood cells had a Y chromosome loss, which is an infrequent but recurrent finding in CLL. FISH of 200 cells found no 13q14 deletion.
2008-06-09 | E-TABM-293 | biostudies-arrayexpress
Project description:A protein signature that could identify graft-versus-tumor (GVT) activity without graft-versus-host disease (GVHD), would allow for customized treatment plans following hematopoietic cell transplantation (HCT). Using orthogonal three-dimensional intact-protein analysis system (IPAS)
coupled with protein tagging and novel systems biology pipeline, we identified a signature of 49 proteins that are significantly increased in the plasma of HCT patients who received donor lymphocyte injection for tumor relapse and develop GVT without GVHD.
2017-05-03 | MSV000081057 | MassIVE
Project description:Notwithstanding advances in the prognostication of chronic lymphocytic leukemia (CLL), it remains challenging to distinguish between patients with favorable and unfavorable treatment-free survival (TFS). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we performed large-scale, unbiased characterization of global intracellular protein expression in a cohort of 40 CLL cases (patients with time to first treatment [TTFT] ≤24 months of sampling) and 40 age- and sex-matched CLL controls (patients with TTFT >24 months since sampling). Expression of 3268 proteins was quantified in the cohort. IGHV mutational status and trisomy 12 were most impactful on the CLL proteome. Intriguingly, comparing our results to three recently performed CLL mass-spectrometry screens, we identified four proteins that are strongly and consistently associated with IGHV mutational status: ZAP70, LMNA, FTL and FTH1. Additionally, we found that high intracellular protein levels of THEMIS2, a signaling protein acting downstream of the B-cell receptor, was significantly associated with short TTFT, independently of IGHV and TP53 mutational status (HR 2.47 [95%CI 1.54-3.95], P<0.01). This association was validated on the mRNA and protein level by qPCR and ELISA, respectivelly. Lastly, analysis of an independently generated CLL mass-spectrometry dataset verified the association between THEMIS2 expression and TFS (high THEMIS2, median TFS 4 months, versus low THEMIS2, median TFS not reached, P<0.0001)3. In conclusion, we present a comprehensive characterization of the proteome of untreated CLL. Of note, we identify elevated gene and protein expression of THEMIS2 as putative biomarker of inferior TTFT.
2023-10-24 | PXD036918 | Pride
Project description:Three different cell populations (6 healthy B-lymphocytes, 6 leukemic CLL B-lymphocyte of indolent form and 5 leukemic CLL B-lymphocyte of aggressive form) were stimulated in vitro with an anti-IgM antibody, activating the B-cell receptor (BCR). We analyzed the gene expression at 4 time points (60, 90, 210 and 390 minutes). Each gene expression measurement is performed both in stimulated cells and in control unstimulated cells. For one aggressive CLL case, we silenced expression of DUSP1 by transfecting DUSP1-specific RNAi and, as a control, transfected cells with a non-targeting RNAi. We then stimulated the BCR of these cells and analyzed the gene expression at the same time points in stimulated cells and in control unstimulated cells. B-cells were negatively selected from healthy donors and previously untreated CLL patients. BCR stimulated and unstimulated control B-cells were treated at four time points after stimulation for total RNA extraction and hybridization on Affymetrix microarrays.
2013-01-04 | E-GEOD-39411 | biostudies-arrayexpress