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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. 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.

ORGANISM(S): Mus musculus

SUBMITTER: Kevin Lebrigand

PROVIDER: E-GEOD-32229 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

2012-02-01 | GSE32229 | GEO

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

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

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

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

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

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

2012-01-05 | GSE31814 | GEO

A Biologic Definition of Burkitt's Lymphoma from Transcriptional and Genomic Profiling

Project description:The distinction between the Burkitt lymphoma and diffuse large B-cell lymphoma is imprecise using current diagnostic criteria. We applied transcriptional and genomic profiling to molecularly define Burkitt lymphoma. Gene expression profiling employing Affymetrix GeneChips (U133A) was performed in 220 mature aggressive B-cell lymphomas, including a core group of eight Burkitt lymphomas, which fulfilled all diagnostic criteria of the WHO classification. A molecular signature of Burkitt lymphoma was generated. Chromosomal abnormalities were detected by interphase fluorescence in-situ hybridization and array comparative genomic hybridization. The molecular Burkitt lymphoma signature identified 44 cases. Fifteen of these cases lacked a morphology typical for Burkitt/Burkitt-like lymphoma. The vast majority (88%) of the 176 lymphomas without the molecular Burkitt lymphoma signature represented diffuse large B-cell lymphomas. In 20% of these cases a MYC break was detectable which was associated with complex chromosomal changes. Our molecular definition of Burkitt lymphoma sharpens and extends the spectrum of Burkitt lymphoma. In mature aggressive B-cell lymphomas without a Burkitt lymphoma signature, a chromosomal break in the MYC locus proved to be associated with adverse clinical outcome. Keywords: Gene expression

2006-06-07 | GSE4475 | GEO

Transcription profiling of human Burkitts lymphomas

2008-06-13 | E-GEOD-4475 | biostudies-arrayexpress

Burkitt Lymphoma beyond MYC translocation:N-MYC and DNA methyl transferases dysregulation

Project description:Identification of miRNA differentially expressed between MYC-translocation positive and and MYC-translocation negative Burkitt Lymphoma and their impact on gene expression profile Study of microRNA profile of MYC-translocation positive and MYC-translocation negative Burkitt Lymphoma cases in order to uncover possible differences at the molecular level

2015-08-05 | E-GEOD-71471 | biostudies-arrayexpress

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