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PROVIDER: PRJNA215791 | ENA |
REPOSITORIES: ENA
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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 order to analyze differences in the proteome composition of blood plasma-derived exosomes in chronic lymphocytic leukemia (CLL) versus healthy donors, mass spectrometry was conducted for whole protein lysates of plasma-derived exosomes. Abundance of proteins was compared via label free quantification.
2017-08-09 | PXD004420 | Pride
Project description:To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. Gene expression profiling was performed to determine whether CLL cells induce changes in T cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals. Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of T cells from patients with CLL to healthy individuals .
2008-06-16 | E-GEOD-8835 | biostudies-arrayexpress
Project description:To examine the impact of tumors on the immune system, we compared global gene expression profiles of peripheral blood T cells from previously untreated patients with B cell chronic lymphocytic leukemia (CLL) with those from age-matched healthy donors. Although the cells analyzed were not part of the malignant clone, analysis revealed differentially expressed genes, mainly involved in cell differentiation in CD4 cells and defects in cytoskeleton formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL patients. In coculture experiments using CLL cells and T cells from healthy allogeneic donors, similar defects developed in both CD4 and CD8 cells. These changes were induced only with direct contact and were not cytokine mediated. Identification of the specific pathways perturbed in the T cells of cancer-bearing patients will allow us to assess steps to repair these defects, which will likely be required to enhance antitumor immunity. Gene expression profiling was performed to determine whether CLL cells induce changes in T cells in patients with CLL. Keywords: comparative gene expression profiling analysis.
2007-08-22 | GSE8835 | GEO
Project description:Expression data from chronic lymphocytic leukemia (CLL) cells
| PRJNA284372 | ENA
Project description:MiRNA expression is known to be deregulated in chronic lymphocytic leukemia (CLL). To get insight into miRNA expression pattern in CLL, we compaired miRNA expression profiling of peripheral blood-derived CLL cells and the healthy donor, peripheral blood-derived B-lymphocytes. A set of differentially expressed miRNAs was revealed.
2012-05-02 | GSE31599 | GEO
Project description:Exome sequencing data from patient with Chronic Lymphocytic Leukemia. DNA was extracted from sorted B-CLL and T cells or granulocytes.
| EGAD00001005748 | EGA
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:Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment. Gene expression profiling was performed to determine whether Em-TCL1 murine model of chronic lymphocytic leukemia (CLL) mimics T cell defects induced by CLL cells in patients with CLL. Experiment Overall Design: CD4 T cells and CD8 T cells were obtained from spleens of B6C3 and Em-TCL1 transgenic murine model of CLL or from peripheral blood mononuclear cells of previously untreated patients with CLL and healthy individuals (Pubmed ID: 15965501). Gene expression profiling was performed using total RNA and the data were analysed to compare gene expression profile of CLL to healthy within or between the species.
2008-06-17 | E-GEOD-8836 | biostudies-arrayexpress
Project description:MiRNA expression is known to be deregulated in chronic lymphocytic leukemia (CLL). To get insight into miRNA expression pattern in CLL, we compaired miRNA expression profiling of peripheral blood-derived CLL cells and the healthy donor, peripheral blood-derived B-lymphocytes. A set of differentially expressed miRNAs was revealed. MiRNA expression profiling was performed on 18 CLL samples and one sample, which is a pool of 5 RNA samples of healthy donor peripheral blood-derived B-lymphocytes
2012-05-01 | E-GEOD-31599 | biostudies-arrayexpress