Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional responses of mantle cell lymphoma (MCL) after NIK knockdown

ABSTRACT: MCL lines were treated with or without 100ng/ml doxycycline for 7 days This experiment is designed to see if shRNA-mediated knockdown of NIK downregulates NFKB signaling in MCL lines with mutations in upstream regulators of the alternative pathway (TRAF2 & TRAF3)

ORGANISM(S): Homo sapiens

PROVIDER: GSE52435 | GEO | 2013/12/01

SECONDARY ACCESSION(S): PRJNA228923

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional responses of mantle cell lymphoma (MCL) after NIK knockdown

Project description:MCL lines were treated with or without 100ng/ml doxycycline for 7 days This experiment is designed to see if shRNA-mediated knockdown of NIK downregulates NFKB signaling in MCL lines with mutations in upstream regulators of the alternative pathway (TRAF2 & TRAF3) MCL cells carrying inducible non-targeting control (NTC) shRNA, NIKshRNA#1 (NIKsh#1), or NIKshRNA#2 (NIKsh#2) were seeded in 6well dishes and treated for 7 days with or without 100ng/ml doxycycline.

2013-12-01 | E-GEOD-52435 | biostudies-arrayexpress

Transcriptional responses of mantle cell lymphoma (MCL) lines to PKC inhibition

Project description:MCL lines (biological replicates) were treated with DMSO or 2.5uM Sotrastaurin for 3hrs This experiment is designed to see if a common set of genes is affected by Sotrastaurin (STN) treatment in STN-sensitive and STN-insensitive MCL lines.

2013-12-01 | GSE42549 | GEO

Transcriptional responses of mantle cell lymphoma (MCL) lines to IKKB inhibition

Project description:MCL cell lines were treated with DMSO or 5uM AFN700 for 20hrs This experiment is designed to see if NFKB-target genes are downregulated by inhibition of IKKB in MCL cell lines that are insensitive to ibrutinib (BTK inhibitor) or sotrastaurin (PKC inhibitor)

2013-12-01 | GSE52434 | GEO

Classical and/or alternative NF-kB pathway activation in multiple myeloma pathogenesis

Project description: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. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, TACI) selectively activate the classical pathway. However, most mutations affecting NIK level (NIK, TRAF2, TRAF3, cIAP1&2, CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteosomal degradation of NIK in MM. Third, using transfection to selectively activate the classical or alternative NFKB pathways, we show virtually identical changes in gene expression in one MMCL, whereas the changes are similar albeit non-identical in a second MMCL. Together, our results suggest that MM tumors can achieve increased autonomy from the bone marrow microenvironment by mutations that activate either NFKB pathway.

2009-09-11 | GSE18047 | GEO

Transcriptional responses of mantle cell lymphoma (MCL) lines to PKC inhibition

2013-12-01 | E-GEOD-42549 | biostudies-arrayexpress

Transcriptional responses of mantle cell lymphoma (MCL) lines to IKKB inhibition

2013-12-01 | E-GEOD-52434 | biostudies-arrayexpress

Expression data from 3 gamma-secretase or mock-treated mantle cell lymphoma (MCL) cell lines

Project description:We identified recurrent NOTCH1 mutations in 12% of MCLs. 2 out of 10 tested MCL cell lines (Rec-1 and SP-49) were sensitive to inhibition of the NOTCH pathway by gamma-secretase inhibition. The aim of this study was to identify transcriptional targets of NOTCH signaling in MCL. 3 MCL cell lines (Mino, Rec-1, SP-49 treated with Mock or 1 micromolar compound E for 24 hours, in duplicate.

2011-12-22 | E-GEOD-34602 | biostudies-arrayexpress

Expression data from 3 gamma-secretase or mock-treated mantle cell lymphoma (MCL) cell lines

2011-12-22 | GSE34602 | GEO

Pharmacological and genomic profiling identifies NFκB-targeted treatment strategies for mantle cell lymphoma

Project description:Mantle cell lymphoma (MCL) is an aggressive malignancy characterized by poor prognosis, underscoring the need for novel therapeutic strategies1. In this study, we employed large-scale pharmacological profiling of 16 pathway inhibitors across more than 100 hematological cell line models to identify novel therapeutic approaches. This screen identified a subset of MCL cell lines that were highly sensitive to the B-cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin (STN), which are currently in clinical trials2, 3. Sensitive MCL models exhibited chronic activation of the CARD11-BCL10-MALT1 (CBM) complex and dependency on downstream classical NFκB signaling. In contrast, insensitive cell lines displayed activation of the alternative NFκB pathway. Massively parallel transcriptome sequencing identified mutations in negative regulators of the alternative NFκB pathway in ibrutinib-insensitive cell lines. Notably, sequencing of 165 MCL patient samples revealed that components of the alternative NFκB pathway, particularly TRAF2 and BIRC3, are mutated in roughly 15% of MCL patients. Functional analyses of patient-derived BIRC3 mutant alleles indicated that these are loss-of-function mutants that constitutively activate alternative NFκB signaling. While being associated with insensitivity to ibrutinib, genetic lesions in the alternative pathway conferred dependence on NIK, a kinase that mediates signaling downstream of the TRAF2/3-BIRC2/3 complex. Thus, NIK represents a novel therapeutic target for MCL treatment, particularly for tumors refractory to BCR pathway inhibitors. Collectively, these findings reveal a pattern of mutually exclusive activation of the CBM-NFκB or alternative NIK-NFκB pathways in MCL and provide critical insights into patient stratification strategies for NFκB-pathway targeted agents.

| EGAS00001000622 | EGA

Transcription profiling of mouse lymph node derived B cells from Traf2 and Traf3 B cell knockout mice and Baff tg mice

Project description:Tumor necrosis factor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a co-operative and non-redundant manner to suppress nuclear factor-ÎºB2 (NF-ÎºB2) activation, gene expression and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell activating factor of the tumor necrosis factor family). This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. We wished to investigate the effect on gene expression in B cells which lacked the negative regulators TRAF2 and TRAF3, and hence had hyperactive NF-kB2 signalling. As Baff-tg mice display a similar phenotype, and have a genetic modification which acts in the same pathway, yet further up, than TRAF2 and TRAF3, we wished to compare and contrast Baff-tg B cells with TRAF2 and TRAF3 deficient B cells. This analysis should identify genes that are important in B cell survival. Experiment Overall Design: Lymph node B cells were purified from Traf2 B cell knockout mice, Traf3 B cell knockout mice, Baff-tg mice and respective controls. RNA was extracted and hybridised to Affymetrix 430 2.0 Mouse Genome Arrays. Samples were processed and hence analysed on three spearate days. Day 1 two control mice: Traf2lox/lox pool and CD19-cretg were compared to two knockout mice: Traf2DB 80 and Traf3DB 94. On Day 2 three control mice: Traf2lox/lox 77, Traf2lox/lox 79 and Traf3lox/lox 97 were compared to two knockout mice: Traf2DB 76 and Traf3DB 01. On Day 3 three control mice: WT33, WT34, WT35 were compared to three Baff-tg mice: Baff-tg 99, Baff-tg 100, Baff-tg 101.

2008-04-07 | E-GEOD-10422 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data