B lymphoma from TRAF3-deficient mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48818 | GEO | 2014/09/11
SECONDARY ACCESSION(S): PRJNA211835
REPOSITORIES: GEO
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Project description:Spleen samples with B lymphoma from TRAF3 knockout mice compared with littermate controls 3 lymphoma samples, 4 control samples
2014-09-11 | E-GEOD-48818 | biostudies-arrayexpress
Project description:Specific deletion of the tumor suppressor gene TRAF3 from B lymphocytes (B-TRAF3-/-) in mice leads to prolonged survival of mature B cells and expanded B cell compartment in secondary lymphoid organs. To understand the metabolic basis of the prolonged survival of TRAF3-/- B cells, we performed LC-MS-based metabolome and lipidome screening with resting splenic B cells of young adult B-TRAF3-/- and littermate control (LMC) mice. Our metabolome screening data showed that phosphocholine (P-Cho) and phosphoethanolamine, two small metabolites and precursors of phospholipids, were significantly increased in TRAF3-/- B cells. Consistently, our lipidome screening revealed markedly elevated levels of multiple species of phosphatidylcholine (PC) and phosphatidylethanolamine in TRAF3-/- B cells. Interestingly, our transcriptome profiling identified Chka, the rate-limiting enzyme of choline metabolism, as a significantly up-regulated gene in TRAF3-/- B cells. To investigate the functional importance of elevated choline metabolism, we examined the effects of two Chka inhibitors, MN58B and RSM932A. We found that both MN58B and RSM932A potently induced cell apoptosis in TRAF3-/- mouse B lymphoma and human multiple myeloma cell lines in vitro. Furthermore, in vivo administration of MN58B and RSM932A partially decreased the spleen size and B cell compartment in B-TRAF3-/- mice. Together, our results indicate that TRAF3 specifically re-engineers the P-Cho-PC-PE metabolic pathways to regulate mature B cell survival. Our findings also suggest that the P-Cho-PC-PE metabolic pathways have diagnostic and therapeutic value for B cell malignancies with TRAF3 deletion or relevant mutations.
2019-11-13 | GSE113920 | GEO
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-κB2 (NF-κB2) 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
Project description:Treatment of diffuse large B-cell lymphoma (DLBCL) remains challenging due to extensive molecular, clinical, and pathological heterogeneity. Here, we report recurrent focal deletions of the chr14q32.31-32 locus, including TRAF3, a negative regulator of NF-κB signaling, in a cohort of uniformly-treated de novo DLBCL (24/324 cases). Integrative analysis uncovered a correlation between TRAF3 copy number loss and TRAF3 reduced expression. CRISPR-mediated TRAF3 loss-of-function (LOF) in DLBCL cell lines enhanced non-canonical NF-κB (NC NF-κB) signaling, rendering cells sensitive to shRNA-induced knockdown of the central NC NF-κB kinase, NIK. NIK pharmacological inhibitors differentially impaired proliferation, and induced apoptosis of TRAF3 LOF cells, further suggesting an acquired onco-addiction to NC NF-κB. Beyond these cell-intrinsic effects, co-culturing of TRAF3 LOF DLBCL cells with primary human CD8+ T-cells revealed an impairment in effector marker induction (Granzyme B, IFNγ) and proliferation in the latter. Accordingly, a reduction in T-cell infiltrates was observed in the microenvironment of TRAF3-low expressing primary DLBCL tumor samples. Neutralization of IL10 produced by TRAF3 LOF cells restored and enhanced GZMB and IFNγ expression in co-cultured CD8+ T-cells. Our findings demonstrate a direct relationship between TRAF3 genetic alterations and NC NF-κB activation, favoring pro-oncogenic cell-intrinsic effects and immune-evasive mechanisms, and highlight NIK as a therapeutic target in defined subset of DLBCL.
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Project description:Loss of Traf3 caused a dramatic induction of innate immune response genes. Antigen presentation, interferon response genes and genes responsible for foreign DNA and RNA recognition were strongly upregulated by deletion of Traf3, but KO of p100 in Traf3 KO samples reversed the activation of these pathways. We did not detect any stimulation by Traf3 KO of those signaling pathways classically involved in proliferation, including PI3K/AKT, JNK, TGF-beta, WNT and Hippo
2020-03-31 | GSE147767 | GEO
Project description:Intrahepatic cholangiocarcinoma (ICC) is known to have a poor prognosis among primary liver cancers. We created a mouse model of cholangiocarcinogenesis by specifically deleting Pten and Traf3 in the liver. RNA sequence was performed with RNA extracted from the liver of mice lacking liver-specific Pten and Traf3.
2022-03-31 | GSE178418 | GEO
Project description:RNA sequence data from liver-specific Pten/Traf3 knockout mice
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Project description:Intrahepatic cholangiocarcinoma (ICC) is known to have a poor prognosis among primary liver cancers. We created a mouse model of cholangiocarcinogenesis by specifically deleting Pten and Traf3 in the liver. single cell RNA sequence was performed with RNA extracted from the liver of mice lacking liver-specific Pten and Traf3.
2022-03-31 | GSE178814 | GEO
Project description:Intrahepatic cholangiocarcinoma (ICC) is known to have a poor prognosis among primary liver cancers. We created a vitro model of cholangiocarcinogenesis using HepG2 with specifically knockdown of Pten and Traf3. RNA sequence was performed with RNA extracted from the liver of mice lacking liver-specific Pten and Traf3.
2022-03-31 | GSE184276 | GEO
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-κB2 (NF-κB2) 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. Keywords: Genetic modification
2008-02-28 | GSE10422 | GEO