Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA374356 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Protective interactions with bystander cells in micro-environmental niches such as lymph nodes (LNs) contribute to survival and therapy resistance of chronic lymphocytic leukemia (CLL) cells. This is caused by a shift in expression of BCL-2 family members. Pro-survival proteins BCL-XL, BFL-1, and MCL-1 are upregulated by LN-residing T cells through CD40L interaction, presumably via NF-κB signaling. Macrophages also reside in the LN, and are assumed to provide important supportive functions for CLL cells. However, if and how macrophages are able to induce survival is incompletely known. We first established that macrophages induced survival due to an exclusive upregulation of MCL-1. Next, we investigated the mechanism underlying MCL-1 induction by macrophages in comparison with CD40L. Genome-wide expression profiling of in vitro macrophage- and CD40L-stimulated CLL cells indicated activation of the PI3K-AKT-mTOR pathway, which was confirmed in ex vivo CLL LN material. Inhibition of PI3K-AKT-mTOR signaling abrogated MCL-1 upregulation and survival by macrophages as well asCD40 stimulation. MCL-1 can be regulated at multiple levels, and we established that AKT leads to increased MCL-1 translation, but does not affect MCL-1 transcription or protein stabilization. Furthermore, among macrophage-secreted factors that could activate AKT, we found that induction of MCL-1 and survival critically depended on C-C Motif Chemokine Receptor-1 (CCR1). In conclusion, this study indicates that two distinct micro-environmental factors, CD40L and macrophages, signal via CCR1 to induce AKT activation resulting in translational stabilization of MCL-1, and hence can contribute to CLL cell survival.
2017-02-11 | GSE94801 | GEO
Project description:This dataset includes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) cases reviewed for pathology consensus at the University Health Network. Also included are challenging cases of small B-cell lymphomas without pathology consensus. Methylation array profiling was performed using the Infinium MethylationEPIC array platform. Unprocessed IDAT files and matrix with beta values (beta_TGL51_illumina_annot_geo.txt) are provided.
2021-09-02 | GSE171424 | GEO
Project description:The two B-cell non-Hodgkin lymphoma (NHL) entities chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) show recurrent chromosomal gains of 3q25 q29, 12q13 q14 and 18q21-q22. The pathomechanisms affected by these aberrations are not understood. The aim of this study was to identify genes, located within these gained regions, which control cell death and cell survival of MCL and CLL cancer cells. Blood samples from 24 CLL and 6 MCL patients as well as 6 cell lines representing both malignancies were analyzed by gene expression profiling. By comparison of genomic DNA and gene expression, 72 candidate genes were identified. We performed a limited RNAi screen with these candidates in order to identify genes affecting cell survival. CCDC50, SERPINI2 and SMARCC2 mediated a reduction of cell viability in primary CLL cells as well as in cell lines. Gene knock down and a NFkB reporter gene assay revealed that CCDC50 is required for survival in MCL and CLL cells and controls NFkB signaling. This SuperSeries is composed of the SubSeries listed below.
2010-06-03 | GSE16413 | GEO
Project description:THis is a simple ordinary differential equation model describing chemoimmunotherapy of chronic lymphocytic leukemia, including descriptions of the combinatorial effects of chemotherapy and adoptive cellular immunotherapy.
2021-10-08 | BIOMD0000000879 | BioModels
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:High Expression of Lymphocyte-Activation Gene 3 in Chronic Lymphocytic Leukemia Cells is Associated with Unmutated IGHV and Reduced Treatment-Free Survival
2009-09-17 | E-TABM-696 | biostudies-arrayexpress
Project description:We demonstrated that the microenvironment-dependent secretion of IL32β was controlled by the CD40L/NFKB2 axis whereas its tumor specificity was the consequence of IL32 promoter hypomethylation in MCL. Through the secretion of IL32β, the tumor was able to corrupt its microenvironment through the polarization of monocytes into specific MCL-associated macrophages, which in turn favor tumor survival. We next highlighted that while IL32β-stimulated macrophages secreted several protumoral factors, they supported tumor survival through a soluble dialog, mostly driven by BAFF. Finally, we demonstrated the efficacy of selective NIK/alternative-NFkB inhibition to counteract both microenvironment-dependent induction of IL32β and BAFF-dependent survival of MCL cells.
2022-12-06 | GSE179766 | GEO
Project description:We demonstrated that the microenvironment-dependent secretion of IL32β was controlled by the CD40L/NFKB2 axis whereas its tumor specificity was the consequence of IL32 promoter hypomethylation in MCL. Through the secretion of IL32β, the tumor was able to corrupt its microenvironment through the polarization of monocytes into specific MCL-associated macrophages, which in turn favor tumor survival. We next highlighted that while IL32β-stimulated macrophages secreted several protumoral factors, they supported tumor survival through a soluble dialog, mostly driven by BAFF. Finally, we demonstrated the efficacy of selective NIK/alternative-NFkB inhibition to counteract both microenvironment-dependent induction of IL32β and BAFF-dependent survival of MCL cells.
2022-12-06 | GSE179636 | GEO
Project description:Background:A subset of hematological cancer patients is refractory to treatment or suffer relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment via microenvironment interaction. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Results: Using RNAseq and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma (MCL) cells stably adhered to stromal cells or in suspension within a co-culture and in separate culture as well as mouse MS-5 stromal cells in co-culture or in separate culture. 1050 differentially expressed transcripts in adherent MCL cells identified 24 functional categories that together represent four main functional themes, anti-apoptosis, B-cell signaling, cell adhesion/migration and early mitosis. Comparison with previous MCL and chronic lymphocytic leukemia (CLL) patient data identified 116 genes that are differentially regulated in all three studies. From these genes we suggest a gene signature (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE, SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion mediated microenvironment signaling in MCL/ CLL cells. Conclusions: The model system developed and characterized here together with suggested signature genes can be used in future studies of pathways that mediate increased cancer cell survival and drug resistance mechanisms.
2018-06-12 | GSE99501 | GEO