Gene expression profile of Nurse-Like Cells (NLC) derived from chronic lymphocytic leukemia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42733 | GEO | 2012/12/11
SECONDARY ACCESSION(S): PRJNA183511
REPOSITORIES: GEO
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Project description:The study of the roles of macrophages in the microenvironment of cancer cells (tumor-associated macrophages, TAM) has gained deep insight over the recent years. Here, we describe gene expression profile of chronic lymphocytic leukemia (CLL)-associated macrophages, also called nurse-like cells (NLC), derived from in vitro co-cultures system. We define these NLC as M2-oriented, TAM-like specific subset of macrophages, with very few inter-individual variations in gene expression profiles. CLL patients PBMC were isolated and cultured for 15 days in vitro. NLC were then isolated, mRNA were purified and hybridized on Affymetrix U133 plus 2.0 chips. Data were normalized by RMA5
2012-12-11 | E-GEOD-42733 | biostudies-arrayexpress
Project description:Our project is based on the hypothesis that ibrutinib could interfere with chronic lymphocytic leukemia (CLL) microenvironment, modulating the immune response. The aim of the project is to understand if and how ibrutinib modifies the tumor microenvironment accessory cells in CLL, specifically nurse like cells (NLC).
2020-09-18 | GSE142292 | GEO
Project description:In the marrow and lymphatic tissues, chronic lymphocytic leukemia (CLL) cells interact with accessory cells that constitute the leukemia microenvironment. In lymphatic tissues, CLL cells are interspersed with CD68+ nurselike cells (NLC) and T cells. However, the mechanism regulating co-localization of CLL cells and these accessory cells are largely unknown. To dissect the molecular cross-talk between CLL and NLC, we profiled the gene expression of CD19-purified CLL cells before and after co-culture with NLC. NLC co-culture induced high-level expression of B cell maturation antigen (BCMA) and two chemoattractants (CCL3, CCL4) by CLL cells. Supernatants from CLL-NLC co-cultures revealed high CCL3/CCL4 protein levels. B cell receptor triggering also induced a robust induction of CCL3 and CCL4 expression by CLL cells, which was almost completely abrogated by a specific Syc inhibitor, R406. High CCL3 and CCL4 plasma levels in CLL patients suggest that activation of this pathway plays a role in vivo. These studies reveal a novel mechanism of cross-talk between CLL cells and their microenvironment, namely the secretion of two T cell chemokines by CLL-NLC interaction and in response to BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells, and thereby actively create a microenvironment that favors their growth and survival. Experiment Overall Design: The microarray part of this study included samples of CLL cells from 9 different patients, analyzed directly after purification and after 14 days of co-culture with Nurse like cells . Experiment Overall Design: In detail, RNA was isolated from CD19-purified CLL cells from 9 different patientsâ peripheral blood mononuclear cells (PBMC) after Ficoll separation and subsequent purification with CD19 MicroBeads and the MACS® technology according to the manufacturerâs instructions (Miltenyi Biotec, Bergisch Gladbach, Germany). For comparison, the same CLL cell samples were co-cultured for 14 days with NLC (""14d NLC"").""). For co-culture with NLC, PBMC from patients with CLL were suspended in complete RPMI medium (RPMI1640 with 10% FCS, penicillin-streptomycin-glutamine, Gibco-BRL, Grand Island, NY) to a concentration of 1 x 107/ml (total 20 ml) and incubated for 14 days in 75 cm2 tissue culture flasks (Techno Plastic Products AG) as described previously3. Nonadherent lymphoid cells then were removed and the NLC layer was washed two times with phosphate-buffered saline (PBS). The complete removal of lymphocytes was verified by phase-contrast microscopy. The nonadherent cells together with the wash-fractions were then used for RNA preparation. In order to purify the CLL B cells prior to RNA isolation, CLL PBMC were passed through a 30 µm nylon mesh to obtain a single-cell suspension. Then CLL B cells were purified with CD19 MicroBeads. Subsequently RNA was extracted.
2009-01-13 | E-GEOD-13811 | biostudies-arrayexpress
Project description:In the marrow and lymphatic tissues, chronic lymphocytic leukemia (CLL) cells interact with accessory cells that constitute the leukemia microenvironment. In lymphatic tissues, CLL cells are interspersed with CD68+ nurselike cells (NLC) and T cells. However, the mechanism regulating co-localization of CLL cells and these accessory cells are largely unknown. To dissect the molecular cross-talk between CLL and NLC, we profiled the gene expression of CD19-purified CLL cells before and after co-culture with NLC. NLC co-culture induced high-level expression of B cell maturation antigen (BCMA) and two chemoattractants (CCL3, CCL4) by CLL cells. Supernatants from CLL-NLC co-cultures revealed high CCL3/CCL4 protein levels. B cell receptor triggering also induced a robust induction of CCL3 and CCL4 expression by CLL cells, which was almost completely abrogated by a specific Syc inhibitor, R406. High CCL3 and CCL4 plasma levels in CLL patients suggest that activation of this pathway plays a role in vivo. These studies reveal a novel mechanism of cross-talk between CLL cells and their microenvironment, namely the secretion of two T cell chemokines by CLL-NLC interaction and in response to BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells, and thereby actively create a microenvironment that favors their growth and survival.
2008-12-11 | GSE13811 | GEO
Project description:NLC are generated from the in vitro culture of PBMC from CLL patients. These NLC derived from the differentiation of blood monocytes in contact with blood leukemic cells, We used microarrays to detail the global programme of NLC gene expression compared to monocytes gene expression.
2016-10-12 | GSE87813 | GEO
Project description:The development and progression of CLL are dependent upon a complex microenvironmental network of cellular and molecular signals. As an example the in vitro survival of CLL cells is supported by nurse-like cells, which have been identified as a CLL-specific tumor-associated macrophage (TAM) population. However little is known regarding the role of TAMs in CLL development and progression. In the CLL xenograft model based on the engraftment of MEC1 human CLL cell line into Rag2-/-γc-/-, we analyzed the whole-genome transcriptome of TAMs isolated from the bone marrow. We found an enrichment of genes involved in inflammation and interaction between TAMs and leukemic cells. Rag2-/-γc-/- were injected intravenously with MEC1 cells and sacrificed at early stage of leukemia with age-matched wt Rag2-/-γc-/- mice (n=3/group). RNA was isolated from bone marrow murine monocytes/macrophages purified by magnetic separation and processed for illumina whole-genome gene expression direct-hybridization assay.
2016-02-16 | E-GEOD-57785 | 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:Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of malignant CD5+ B lymphocytes (CLL cells) in the peripheral blood, and their progressive infiltration in lymphoid organs. MMP-9 plays an important role in cell migration and survival, contributes to CLL pathogenesis by proteolytic and non-proteolytic mechanisms and may constitutive a therapeutic target. We used Affimetrix microarray technology to characterize the global gene expression profile of chronic lymphocytic leukemia (CLL) cells upon MMP-9 transfection. The aim was to establish whether MMP-9 regulates gene expression and to identify new therapeutic targets in CLL.
2016-03-21 | GSE78174 | GEO
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:The development and progression of CLL are dependent upon a complex microenvironmental network of cellular and molecular signals. As an example the in vitro survival of CLL cells is supported by nurse-like cells, which have been identified as a CLL-specific tumor-associated macrophage (TAM) population. However little is known regarding the role of TAMs in CLL development and progression. In the CLL xenograft model based on the engraftment of MEC1 human CLL cell line into Rag2-/-γc-/-, we analyzed the whole-genome transcriptome of TAMs isolated from the bone marrow. We found an enrichment of genes involved in inflammation and interaction between TAMs and leukemic cells.
2016-02-16 | GSE57785 | GEO