Cyclin D1 Transgenic Mice with Bim-deficient B-cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE52214 | GEO | 2014/02/05
SECONDARY ACCESSION(S): PRJNA227163
REPOSITORIES: GEO
Similar Datasets
Project description:Expression analysis from a genetically engineered mouse model of mantle cell lymphoma (MCL) Gene expression was measured in fourteen mice that overexpress cyclin D1 and delete Bim in their B cells and that were stimulated with sheep red blood cells (SRBC) and irradiation (I), pristane (P) or only SRBC weekly (A). Mice that developed disease based on histopathologic criteria were compared to ones that did not. An additional seven stimulated mice that only overexpressed cyclin D1 were used to estimate the data set variance.
2014-02-05 | E-GEOD-52214 | biostudies-arrayexpress
Project description:Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Cyclin D1 is a major cell cycle regulator and also has a role in transcription, but the effect of the latter in tumorigenesis remains largely unknown. Here, we investigated the transcriptional role of cyclin D1 in MCL and its impact on the pathogenesis of this neoplasm. Integrating genome-wide expression analysis of cyclin D1-silenced and overexpressing cells with cyclin D1 chromatin binding profiles, we identified a cyclin D1-activated transcriptional program in MCL cells.
2021-06-30 | GSE144106 | GEO
Project description:Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Cyclin D1 is a major cell cycle regulator and also has a role in transcription, but the effect of the latter in tumorigenesis remains largely unknown. Here, we investigated the transcriptional role of cyclin D1 in MCL and its impact on the pathogenesis of this neoplasm. Integrating genome-wide expression analysis of cyclin D1-silenced and overexpressing cells with cyclin D1 chromatin binding profiles, we identified a cyclin D1-activated transcriptional program in MCL cells. We used microarrays to analyze the genome-wide expression modulation in cyclin D1 overexpression models established in the cyclin D1-negative lymphoblastoid cell line JVM13.
2021-06-30 | GSE144095 | GEO
Project description: Not available
| S-EPMC3916879 | biostudies-other
Project description:We provide RNA sequencing data for a Ccnd2/p53/Mb1Cre mouse model (Mb1Cre is active from pre-B cells onwards). This mouse model features Ccnd2 overexpression and p53 loss in B-cells, and develops tumors that resembles Mantle cell lymphoma (MCL). These Ccnd2/p53/Mb1Cre mice develop both non-MCL and MCL-like lymphomas and RNA samples from both groups were sequenced. Fresh lymphoma cells (5x10exp6) were frozen in 700 µl of QIAZOL and stored in -80°C. RNA was prepared using a miRNeasy mini kit (Qiagen).
2021-08-10 | GSE175568 | GEO
Project description:The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. Dose response involving 20 samples. Two replicates for each cell line, 4 cell lines sensitive to ABT-737 and 6 cell lines resistant to ABT-737. Mantel cell lymphoma cell lines sensitive to ABT-737 vs. Mantel cell lymphoma cell lines resistant to ABT-737
2011-07-01 | E-GEOD-25613 | biostudies-arrayexpress
Project description:The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL.
2011-07-01 | GSE25613 | GEO
Project description:Mantle Cell lymphoma (MCL) were treated with the BTK inhibitor 1mM CC-292 for 48h We used microarrays to uncover the mechanisms underlying CC-292 activity in Mantle Cell lymphoma (MCL)
2017-09-01 | GSE94328 | GEO
Project description:In this study we compared the expression of 30215 genes in mantle cell lymphoma-initiating cells (MCL-ICs) with mantle cell lymphoma-non-initiating cells (MCL-non-ICs) and B-cells from healthy donor Three samples each of MCL-ICs and MCL-non-ICs were isolated from aphresis of 3 mantle cell lymphoma primary patient samples and 2 samples of CD19+ Bcells isolated from buffy coats of healthy donor Microarray include both coding and non-coding transcripts but only mRNA coding transcript were included in this study.
2014-08-02 | E-GEOD-60023 | biostudies-arrayexpress
Project description:Cyclin D1-negative mantle cell lymphomas (MCL) are not well characterized, in part due to the difficulties in their recognition. SOX11 has been recently identified as a reliable biomarker of MCL, also expressed in the cyclin D1-negative variant. We investigated 40 lymphomas with MCL morphology and immunophenotype, negative for cyclin D1 expression/t(11;14)(q13;q32) but SOX11-positive. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and had a poor outcome (5-year overall survival 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18/22 cases, in particular with light chains (10 IGK@, 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2 and CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1-negative SOX11-positive MCL analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11-positive MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome to the patients. This comprehensive characterization of a large series of cyclin D1-negative MCL indicates that these tumors are clinically and biologically similar to the conventional cyclin D1-positive MCL and provides a basis for the proper identification and clinical management of these patients. Copy number analysis of Agilent 1*1M arrays was performed for 27 MCL, with sex-matched control DNAs and without duplicates or dye-swapt.
2012-12-19 | E-GEOD-42917 | biostudies-arrayexpress