Filters
Technology
Platform
GSE42204
Homo sapiens
63 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
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.
Publication Title
A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Notably, deletion or uniparental disomy of chromosome 7q were detected in 39% of SMZLs but in only 9 of 170 (5%) mature B-cell lymphomas (p<10-6). The presence of unmutated IgVH genes, genomic complexity, 17p13-P53 deletion and 8q gain including MYC gene, but not 7q deletion, were correlated with shorter overall survival. Extensive mapping analyses narrowed down the commonly deleted region to 2.7 Mb. in 7q32.1-q32.2 from SND1 to COPG2 genes. High-throughput sequencing analysis of the 7q32 deleted segment in SMZL cells did not identify bi-allelic deletions, insertions or clear pathogenic mutations, but detected six single nucleotide changes in IRF5 (n=2), TMEM209 (n=2), CALU (n=1) and ZC3HC1 (n=1). Comparative expression analysis found that IRF5, TMEM209 and CALU genes had down-regulated expression in lymphomas with 7q32 deletion vs. non-deleted tumors. Ectopic expression of IRF5 in marginal-zone lymphoma cells decreased cell proliferation and induced apoptosis. These results indicate that small deletions, insertions and/or point mutations inactivating genes within 7q32 are not common events in SMZL. Further studies are required to evaluate the putative role of IRF5 in SMZL pathogenesis.
Publication Title
High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Mapping 250K Sty2 SNP Array (mapping250ksty), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Mapping 250K Sty2 SNP Array (mapping250ksty), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Histone deacetylases (HDACs) have been identified as therapeutic targets due to regulatory function in DNA structure and organization. We have analyzed the role of the LBH589, a novel pan inhibitor of class I and II HDACs, in Acute Lymphoblastic Leukemia. In vitro, LBH589 was shown to induce a dose dependent antiproliferative and apoptotic effect which was associated with an increase in the acetylation of H3 and H4 histone acetylation which was uniformly in every genetic subgroup of ALL. In vivo administration of LBH589 in BALB/c-RAG2-/-c-/- mice in which T and B-cell leukemic cell lines were injected induced a significant reduction in tumor growth (TOM-1, p<0.01 and MOLT-4 p<0.05). Leukemic cells from patients were employed to establish a xenograft model of human leukemia in BALB/c-RAG2-/-c-/- mice and further transplanted in consecutive generations of mice. Treatment of these xenografts with LBH589 induced an increase in the acetylation of H3 and H4 and prolonged the survival of mice in comparison with the animals treated with Vincristine and Dexametasone (p<0.05) and this effect was significantly higher when LBH589 was combined with Vincristine and Dexametasone (p<0.001). Our results that the use of LBH589 in combination with standard chemotherapy represents an attractive option for treatment of patients with ALL.
Publication Title
Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hepatocyte IKK deficiency worsens HCFD-induced NASH in male but not female mice.
Publication Title
Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 103 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 103 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Marked expression differences in intraclonal fractions suggest potential pathological and therapeutic relevance of studying intraclonal CLL fractions as compared to bulk cells.
Publication Title
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
Ion Torrent Proton
Description
We conditionally knocked out both Yap and Taz in cranial neural crest (CNC) using the Wnt1Cre driver and sequenced mRNA from embryonic day 10.5 mandibles. Overall design: Examination of mRNA level in E10.5 mandibular tissues from control and Wnt1Cre Taz and Yap dKO mutant.
Publication Title
Yap and Taz play a crucial role in neural crest-derived craniofacial development.
Sample Metadata Fields
No sample metadata fields
View Samples