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Expression of NrasQ61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice

ABSTRACT: Expression of NrasQ61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice

PROVIDER: PRJNA643506 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12125427.fastq.gz	Fastqsanger.gz
	SRR12125428.fastq.gz	Fastqsanger.gz
	SRR12125429.fastq.gz	Fastqsanger.gz
	SRR12125430.fastq.gz	Fastqsanger.gz
	SRR12125431.fastq.gz	Fastqsanger.gz

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Expression of NrasQ61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice.

Project description:NRAS Q61 mutations are prevalent in advanced/relapsed multiple myeloma (MM) and correlate with poor patient outcomes. Thus, we generated a novel MM model by conditionally activating expression of endogenous NrasQ61R and an MYC transgene in germinal center (GC) B cells (VQ mice). VQ mice developed a highly malignant MM characterized by a high proliferation index, hyperactivation of extracellular signal-regulated kinase and AKT signaling, impaired hematopoiesis, widespread extramedullary disease, bone lesions, kidney abnormalities, preserved programmed cell death protein 1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain immune-checkpoint pathways, and expression of human high-risk MM gene signatures. VQ MM mice recapitulate most of the biological and clinical features of human advanced/high-risk MM. These MM phenotypes are serially transplantable in syngeneic recipients. Two MM cell lines were also derived to facilitate future genetic manipulations. Combination therapies based on MEK inhibition significantly prolonged the survival of VQ mice with advanced-stage MM. Our study provides a strong rationale to develop MEK inhibition-based therapies for treating advanced/relapsed MM.

| S-EPMC7808014 | biostudies-literature

Expression of NrasQ61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-02 | GSE153628 | GEO

Proteome profiling of mouse germinal center B cells

Project description:Productive B cell responses are critical to protect a host from infection. The spleen and lymph nodes are populated by resting follicular B cells, which can enter germinal centers upon antigen encounter. Once in the germinal center, B cells migrate between the dark and light zones, where they undergo somatic hypermutation and selection, respectively. While germinal center B cells have been studied, an intense molecular understanding of these cells/subsets (and the differences between them) is lacking.

2020-04-06 | PXD015524 | Pride

MEF2B LC-MS in normal and malignant germinal center B cells.

Project description:The MEF2B transcription factor is frequently mutated in germinal center (GC)-derived B-cell lymphomas. Its N-terminal mutations drive lymphomagenesis by escaping interaction with transcriptional repressors, while the function of C-terminal mutations remains to be elucidated. Here, we show that MEF2B C-tail is physiologically phosphorylated at specific residues and phosphorylation at S324 is impaired by lymphoma-associated mutations. Lack of phosphorylation at S324 enhances the interaction of MEF2B with the SWI/SNF chromatin remodeling complex, leading to higher transcriptional activity. In addition, these mutants show an increased protein stability due to impaired interaction with the CUL3/KLHL12 ubiquitin complex. Mice expressing a phosphorylation-deficient lymphoma-associated MEF2B mutant display GC enlargement and develop GC-derived lymphomas, when crossed with Bcl2 transgenic mice. These results unveil converging mechanisms of action for a diverse spectrum of MEF2B mutations, all leading to its dysregulation and GC B-cell lymphomagenesis. These assorted mechanisms provide additional opportunities for the development of targeted therapeutic approaches.

2024-08-26 | PXD043998 | Pride

ChIPseq analyses in germinal center B cells

Project description:Germinal center B cells were isolated from human tonsil tissue and crosslinked. ChIP was performed on two distinct pools of germinal center cells, each obtained from 3-5 donors. The experiment includes two biological replicates (germinal center cell pools from different donors). ChIP was performed on both pools and subject to library preparation and sequencing. Input DNA was sequenced for both pools.

2015-12-04 | E-GEOD-68349 | biostudies-arrayexpress

Deletion of miR-15a/16-1 in murine germinal center B-cells.

Project description:Given the tumor suppressing function of miR-15a/16-1 cluster, we studied its role in the germinal center B-cells that give rise to most lymphoid malignancies.

2021-09-09 | PXD021323 | Pride

ChIPseq analyses in germinal center B cells

2015-12-04 | GSE68349 | GEO

The impact of transgenic Uchl1 on gene expression in germinal center B-cells from ImHABCL6 mice

Project description:This study seeks to understand the mechanisms behind enhanced lymphomagenesis observed in ImHABCL6/Uchl1 mice compared with ImHABCL6 alone. As the lymphomas arise from germinal center (GC) B-cells, we reasoned that transgenic Uchl1 altered the gene expression patterns in GC B-cells from these animals. We therefore isolated pre-malignant GC B-cells and examined the gene expression patterns to identify pathways affected by the addition of Uchl1. Germinal center B-cells were isolated from from the spleens of ImHABCL6 and ImHABCL6/Uchl1 mutant mice (n= 3 each) after immunization with sheep red blood cells. RNA was extracted and hybridized to affymetrix mouse 430 2.0 arrays.

2016-01-12 | E-GEOD-76706 | biostudies-arrayexpress

The influence of TFEB on gene expression in primary murine germinal center and non-germinal center B cells

Project description:To investigate TFEB-dependent mRNA expression in murine B cells, FACS-sorted germinal center and non-germinal center B lymphocytes of B-cell-specific conditional TFEB KO mice and control littermates were subjected to RNA sequencing analysis

2024-06-25 | GSE237799 | GEO

Gene Expression Profiles of Germinal Center B Cells

Project description:We report the gene expression profiles of germinal center B cells obtained by FACS analyses of normal human lymph nodes. We used FACS analyses to isolate germinal center B cells from 3 different individuals with one individual sampled twice. The overall goal was simply to identify genes that are highly expressed or silent in these purified cell populations.

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