GEO DataSets

(Submitter supplied) The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier and the lymph node interaction between CLL cells and activated T cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

20 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing

Platform:

GPL18573

52 Samples

Download data

(Submitter supplied) The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier and the lymph node interaction between CLL cells and activated T cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

16 Samples

Download data: TXT

(Submitter supplied) The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier and the lymph node interaction between CLL cells and activated T cells. more...

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by high throughput sequencing

Platform:

GPL18573

16 Samples

Download data: TXT

(Submitter supplied) CLL cells obtained from patients with CLL were treated with MLN4924 to determine whether NFkB transcription targets were affected by the drug.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

22 Samples

Download data: TXT

(Submitter supplied) The nuclear factor kB (NF-kB) subunits RelA, RelB, c-Rel, p50 and p52 are each critical for B-cell development and function. To systematically characterize their responses to canonical and non-canonical NF-kB pathways activity, we performed ChIP-seq analysis in lymphoblastoid B-cells. We found a surprisingly complex NF-kB binding landscape, which did not readily reflect the two NF-kB pathway paradigm. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

10 Samples

Download data: TDF

(Submitter supplied) Malignant cells of Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-κB signaling cascades. Knockdown of a subunit combination corresponding to the non-canonical NF-κB dimer (p52/RelB) in the HL cell line L-1236 caused up-regulation of a set of genes that are associated with hematopoietic and lymphoid organ development. As p52 can form homodimeric complexes, which can repress transcription either alone or in association with transcriptional repressors such as HDAC1, we knocked down p52 alone to analyze its role in gene repression in HL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

12 Samples

Download data: CEL

(Submitter supplied) Malignant Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-κB signaling cascades. We depleted subunit combinations corresponding to either canonical (p50/RelA) or non-canonical (p52/RelB) dimers in the HL cell line L-1236 and performed Affymetrix microarray analysis. Knockdown of p52/RelB affected the expression of a significantly higher number of genes than the knockdown of p50/RelA. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

24 Samples

Download data: CEL

(Submitter supplied) The malignant cells of Hodgkin's lymphoma are characterized by a constitutive activation of the canonical as well as the non-canonical NF-κB signaling cascades. We carried out genome-wide localization and expression profiling experiments in the Hodgkin lymphoma cell line L1236 for the canonical and non-canonical NF-κB pathway components p65, p50 and p52, RelB, respectively. We found that the single NF-κB subunits bind to overlapping, but distinct cistromes by using consensus motifs of high similarity.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL9115

14 Samples

Download data: TXT

(Submitter supplied) While activation of canonical NF-κB signaling through the IKK complex is well studied, few regulators of NIK-dependent non-canonical p52 nuclear translocation have been identified. We discovered a novel role for cyclin dependent kinase 12 (CDK12) in transcriptionally regulating the non-canonical NF-κB pathway. High-content phenotypic screening identified a novel compound, 919278, which inhibits lymphotoxin β receptor (LTβR)- and FN14-dependent p52 nuclear translocation, but not TNFα receptor (TNFR)-mediated, canonical NF-κB p65 nuclear translocation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

56 Samples

Download data: TXT

(Submitter supplied) Comparison of transcriptome between control and NIK-stabilized leukemia stem cells

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL3278

12 Samples

Download data: GPR

(Submitter supplied) Mechanisms of constitutive NF-kappaB signaling in multiple myeloma are unknown. An inhibitor of IkappaB kinase beta (IKKbeta), targeting the classical NF-kappaB pathway, was lethal to many myeloma cell lines. Several had elevated expression of NIK due to genomic alterations or enhanced protein stability while others had inactivating mutations or deletion of TRAF3. Both abnormalities triggered the classical and alternative NF-kappaB pathways. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL3278

4 Samples

Download data: GPR

(Submitter supplied) Mechanisms of constitutive NF-kappaB signaling in multiple myeloma are unknown. An inhibitor of IkappaB kinase beta (IKKbeta), targeting the classical NF-kappaB pathway, was lethal to many myeloma cell lines. Several had elevated expression of NIK due to genomic alterations or enhanced protein stability while others had inactivating mutations or deletion of TRAF3. Both abnormalities triggered the classical and alternative NF-kappaB pathways. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL3278

8 Samples

Download data: GPR

(Submitter supplied) Mutations involving the NFKB pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCL). These mutations, which are thought to be progression events, enable MM tumors to become less dependent on extrinsic bone marrow signals that activate NFKB. Studies on a panel of 50 MMCL provide some clarification of the mechanisms through which these mutations act and the significance of classical vs alternative activation of NFKB. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

18 Samples

Download data: CEL

(Submitter supplied) 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.

Organism:

Homo sapiens

Type:

Expression profiling by array; Third-party reanalysis

Platform:

GPL570

13 Samples

Download data: CEL, TXT, XLSX

(Submitter supplied) Mesenchymal stem cells (MSCs) are known to induce the conversion of activated T-cells into regulatory T-cells in vitro. The marker CD69 is a target of canonical NF-κB signaling and is transiently expressed upon activation; however, stable CD69 expression defines cells with immunoregulatory properties. Given its enormous therapeutic potential, we explored the molecular mechanisms underlying the induction of regulatory cells by MSCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6480

12 Samples

Download data: TXT

(Submitter supplied) To elucidate effects of tumor host interactions in vivo in CLL, purified tumor cells were obtained concurrently from blood, bone marrow and/or lymph node and analyzed by gene expression profiling. Keywords: RNA

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4176

Platform:

GPL570

62 Samples

Download data: CEL

Analysis of purified CLL cells from 24 treatment-naive patients. Samples were obtained concurrently from peripheral blood (PB), bone marrow (BM) and/or lymph nodes (LN). Results provide insight into the role of the tissue microenvironment in the pathogenesis of CLL in vivo.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 24 individual, 3 tissue sets

Platform:

GPL570

Series:

GSE21029

62 Samples

Download data: CEL

(Submitter supplied) Several studies have demonstrated an impaired function of the microenvironment in chronic lymphocytic leukemia (CLL), contributing to immune evasion of tumor cells and disease progression. However, in CLL-like monoclonal B cell lymphocytosis (MBL) studies are scarce. Herein, a comprehensive characterization of the microenvironment in 59 MBL, 56 early stage CLL and 31 healthy controls was conducted. Gene expression arrays and qRT-PCR were performed on RNA from CD4+ peripheral blood cells; serum cytokines were measured by immunoassays and proteomic studies; and flow cytometry was applied to evaluate peripheral blood cytotoxic, Th1, exhausted and effector CD4+ T cells, besides monocytic CD14, CD4 and HLA-DR expression. MBL and early stage CLL showed a similar upregulation of cytotoxic and Th1-related genes, expanded perforin+ and CXCR3+ CD4+ T cells as well as PD1+ CD4+ T cells compared to controls. However, a strong inflammatory response was only identified in MBL: enhanced phagocytosis, pattern recognition receptors, IL8, HMGB1, TREM1 and acute response signaling pathways, along with increased levels of proinflammatory cytokines (remarkably IL8, IFN? and TNF?). Of note, this inflammatory drive was decreased in early stage CLL: diminished proinflammatory cytokines including IFN?, decreased IL8 signaling pathway and lower monocytic HLA-DR expression compared to MBL. Besides, this inflammation was especially reduced in IGHV mutated CLL, involving a decrease of the proinflammatory HMGB1 signaling pathway. These novel findings reveal a different pathophysiology between MBL and CLL, paving the way for the development of pre-emptive immunotherapies with optimal benefits at MBL and early stage CLL, before intense immune exhaustion.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

36 Samples

Download data: CEL