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The class-specific BCR tonic signal modulates lymphomagenesis in a transgenic model of c-myc transgene deregulation.

ABSTRACT: c-myc-3'RR mice developed Burkitt like lymphoma (IgM and IgD positive cells). We wished to study lymphomagenesis in mice carrying a modified B cell receptor with a higher level of tonic signal. The c-myc-3'RR transgene was introduced in a background with an IgH mutation that replaces IgM with IgA expression. Lymphoma arising in double mutant animals mostly carried the phenotype of activated cells, often expressing CD43, and in 10% of cases carrying a plasma cell phenotype. BCR tonic signal appears as a direct modulator of B cell malignancy phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE32229 | GEO | 2012/02/01

SECONDARY ACCESSION(S): PRJNA147201

REPOSITORIES: GEO

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The class-specific BCR tonic signal modulates lymphomagenesis in a transgenic model of c-myc transgene deregulation.

Project description:c-myc-3'RR mice developed Burkitt like lymphoma (IgM and IgD positive cells). We wished to study lymphomagenesis in mice carrying a modified B cell receptor with a higher level of tonic signal. The c-myc-3'RR transgene was introduced in a background with an IgH mutation that replaces IgM with IgA expression. Lymphoma arising in double mutant animals mostly carried the phenotype of activated cells, often expressing CD43, and in 10% of cases carrying a plasma cell phenotype. BCR tonic signal appears as a direct modulator of B cell malignancy phenotype. Burkitt lymphoma (BL) from 4 c-myc-3'RR mice, anaplastic (ANA) lymphoma from 4 c-myc-3'RR mice, CD43 negative lymphoma from 4 c-myc-IgA mice and CD43 positive lymphoma from 4 c-myc-IgA mice were investigated.

2012-02-01 | E-GEOD-32229 | biostudies-arrayexpress

Transcriptoma comparison of mantle cell lymphoma of c-myc-3'RR/Cdk4R24C mice and c-myc-3'RR/p53+/- mice

Project description:Mantle cell lymphoma (MCL) is a B cell malignancy characterized by a monoclonal proliferation of lymphocytes with co-expression of CD5, CD43 but not CD23. We have developed two murine models of MCL-like lymphoma. Breeding Cdk4R24C mice (a knock-in strain that express a Cdk4 protein resistant to inhibition by p16INK4a and other INK4 family members) with c-myc-3’RR transgenic mice (prone to develop aggressive Burkitt lymphoma-like lymphoma) leads in c-myc/Cdk4R24C mice to development of clonal blastoid MCL-like lymphoma. Breeding p53+/- mice with c-myc-3’RR transgenic mice lead to the development of several mature B cell lymphomas including MCL. In this study we compare MCL transcriptomas of c-myc-3'RR/Cdk4R24C mice and c-myc-3'RR/p53+/- mice. B splenocytes from 2 c-myc/Cdk4R24C lymphoma mice and 2 c-myc-3'RR/p53+/- mice were investigated

2013-01-10 | E-GEOD-36808 | biostudies-arrayexpress

Transcriptoma comparison of mantle cell lymphoma of c-myc-3'RR/Cdk4R24C mice and c-myc-3'RR/p53+/- mice

2013-01-10 | GSE36808 | GEO

c-myc-3'RR/p53+/- mice lymphomas

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Elucidation of tonic and activated B cell receptor signaling in Burkitt’s lymphoma provides insights into regulation of cell survival

Project description:B-cell receptor (BCR) signaling promotes the survival of malignant B cells, such as Burkitt’s lymphoma (BL) and the activated B-cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). In contrast to ABC DLBCL, where malignant cells require chronic activation of the BCR for their survival, BL cells are dependent on tonic BCR signaling that is antigen-independent. Elucidation and systematic comparison of tonic and activated BCR signaling led to the identification of novel signaling effectors, among them ACTN4 and ARFGEF2, which were identified as regulators of BL cell survival. As tonic and activated BCR signaling are relevant for important aspects of B cell biology, our study helps in gaining an understanding of BCR-induced processes not only in malignant but potentially also physiological settings.

2016-05-09 | PXD003492 | Pride

c-myc-3'RR/p53+/- mice lymphomas

Project description:c-myc-3'RR mice prone to develop Burkitt lymphoma (BL) were crossed with p53+/- mice in order to obtain c-myc-3'RR/p53+/- mice. These mice develop a wider spectrum of lymphoma including BL, mantle cell lymphoma (MCL) and plasma cell lymphoma (PCL). Transcriptoma analysis of these lymphomas is investigated in these arrays. Four different plasma cell lymphoma (PCL1-4), three different mantle cell lymphoma (MCL1-4) and four different Burkitt lymphoma (BL1-4) were compared.

2012-01-05 | E-GEOD-31814 | biostudies-arrayexpress

A defect of the INK4-Cdk4 checkpoint and c-myc collaborate in blastoid mantle cell lymphoma (MCL)-like lymphoma formation in mice

Project description:Mantle cell lymphoma (MCL) is a B cell malignancy characterized by a monoclonal proliferation of lymphocytes with co-expression of CD5, CD43 but not CD23. Typical MCL are associated with cyclin D1 overexpression, and blastoid MCL variants are associated with c-myc translocations. We have developed a murine model of MCL-like lymphoma by crossing Cdk4R24C mice with c-myc-3’RR transgenic mice. Cdk4R24C mice is a knock-in strain that express a Cdk4 protein resistant to inhibition by p16INK4a and other INK4 family members. Breeding Cdk4R24C mice with c-myc-3’RR transgenic mice prone to develop aggressive Burkitt lymphoma-like lymphoma leads in c-myc/Cdk4R24C mice to development of clonal blastoid MCL-like lymphoma. A defect of the INK4-Cdk4 checkpoint can participate to lymphomagenesis in conjunction with additional alterations of cell cycle control, a situation which might be reminiscent of the development of human blastoid MCL. B splenocytes from 4 c-myc/Cdk4(R24C) lymphoma mice and 4 wt mice were investigated.

2012-02-01 | E-GEOD-32230 | biostudies-arrayexpress

Tonic B-Cell-Receptor Signaling in the Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma

Project description:Multiple types of B-cell lymphoma respond clinically to BTK inhibition, reflecting their dependence on B-cell receptor signaling. The germinal center B-cell subtype of diffuse large B-cell lymphoma resists BTK inhibition, but we found that B-cell receptor elimination in cell lines of this lymphoma type reduced their size and proliferation. Their B-cell receptor signals in a “tonic”, antigen-independent manner, requiring SYK, CD19, and phosphorylation of a specific tyrosine residue in the CD79A immunoreceptor tyrosine-based activation motif domain. The effect of B-cell receptor elimination or inhibition in these lines is proportional to their B-cell receptor surface density and its relative contribution to AKT activity, on which these lines uniformly depend, and is rescued by spontaneous or induced loss of PTEN protein. Biomarker-guided targeting of tonic B-cell receptor signaling may improve treatment of germinal center B-cell lymphoma.

2017-01-01 | GSE80615 | GEO

A defect of the INK4-Cdk4 checkpoint and c-myc collaborate in blastoid mantle cell lymphoma (MCL)-like lymphoma formation in mice

Project description:Mantle cell lymphoma (MCL) is a B cell malignancy characterized by a monoclonal proliferation of lymphocytes with co-expression of CD5, CD43 but not CD23. Typical MCL are associated with cyclin D1 overexpression, and blastoid MCL variants are associated with c-myc translocations. We have developed a murine model of MCL-like lymphoma by crossing Cdk4R24C mice with c-myc-3’RR transgenic mice. Cdk4R24C mice is a knock-in strain that express a Cdk4 protein resistant to inhibition by p16INK4a and other INK4 family members. Breeding Cdk4R24C mice with c-myc-3’RR transgenic mice prone to develop aggressive Burkitt lymphoma-like lymphoma leads in c-myc/Cdk4R24C mice to development of clonal blastoid MCL-like lymphoma. A defect of the INK4-Cdk4 checkpoint can participate to lymphomagenesis in conjunction with additional alterations of cell cycle control, a situation which might be reminiscent of the development of human blastoid MCL.

2012-02-01 | GSE32230 | GEO

Tonic stretch of human lung cells

Project description:We profiled the transcriptomes of 4 human lung cell types that were subjected to control (non-stretch) and 30% tonic stretch conditions for 4 hours and 24 hours.

2016-04-12 | GSE80161 | GEO

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