GEO DataSets

(Submitter supplied) To determine the global transcriptome changes in mantle cell lymphoma cells following treatment with the BET bromodomain antagonist, JQ1 Mantle Cell Lymphoma (MCL) cells exhibit increased B cell receptor and NFkB activities. The BET protein BRD4 is essential for the transcriptional activity of NFkB. Here, we demonstrate that treatment with the BET protein bromodomain antagonist (BA) JQ1 attenuates MYC and CDK4/6, inhibits the nuclear RelA levels and the expression of NFκB target genes including Bruton’s Tyrosine Kinase (BTK) in MCL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9115

12 Samples

Download data: XLS

(Submitter supplied) Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to identify BTK targets by RNA-seq and high-throughput data analysis and verify these genes by quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods Methods: mino/z138 sc4/shbtk stable cell lines were generated with tet-on system vector, small hairpins were induced for 48 hours after doxycycline addition, mRNA was exacted and used for RNA sequencing. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: TXT

(Submitter supplied) The BET (bromodomain and extra terminal) protein family members including BRD4 bind to acetylated lysines on histones and regulate the expression of important oncogenes, e.g., MYC and BCL2. Here we demonstrate the sensitizing effects of the histone hyperacetylation inducing pan-histone deacetylase inhibitor (HDI) panobinostat (PS) on human AML blast progenitor cells (BPCs) to the BET protein inhibitor JQ1. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

2 Samples

Download data: CEL

(Submitter supplied) The bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat induce synergistic anticancer effects We analyzed whether JQ1 and panobinostat synergistically modulate gene expression

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

12 Samples

Download data: CEL

(Submitter supplied) In the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), NF-kappaB activity is essential for viability of the malignant cells and is sustained by constitutive activity of IkappaB kinase (IKK) in the cytoplasm. Here, we report an unexpected role for the bromodomain and extraterminal domain (BET) proteins BRD2 and BRD4 in maintaining oncogenic IKK activity in ABC DLBCL. IKK activity was reduced by small molecules targeting BET proteins as well as by genetic knockdown of BRD2 and BRD4 expression, thereby inhibiting downstream NF-kappaB-driven transcriptional programs and killing ABC DLBCL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL4133 GPL16699

12 Samples

Download data: TXT

(Submitter supplied) MYC-amplified medulloblastomas are highly lethal tumors. BET bromodomain inhibition was recently described to downregulate MYC-associated transcriptional activity in various cancer subtypes. To investigate whether JQ1, a BET bromodomain inhibitor is downregulation MYC and MYC-associated transcriptional activity, we performed global gene expression profiling of five medulloblastomas MYC-amplified patient-derived cell lines treated by JQ1 and the inactive form of JQ1.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS5346

Platform:

GPL6244

10 Samples

Download data: CEL

Analysis of 5 MYC-amplified medulloblastoma cell lines treated with the BET bromodomain inhibitor JQ1. Cell lines derived from medulloblastoma patients. Results provide insight into the potential use of BET bromodomain inhibitors in the treatment of MYC-amplified medulloblastomas.

Organism:

Homo sapiens

Type:

Expression profiling by array, count, 2 agent, 5 cell line sets

Platform:

GPL6244

Series:

GSE51020

10 Samples

Download data: CEL

(Submitter supplied) We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL11154

16 Samples

Download data: TXT

(Submitter supplied) We provide direct in vivo evidence for activation of the BCR and canonical NF-KB pathways in MCL that, in the absence of activating mutations, is dependent on the lymph node microenvironment. This finding provides a mechanistic explanation for the surprising efficacy of ibrutinib for the treatment of this type of lymphoma. Mutations in components of the BCR and NF-KB pathways are associated with cell-autonomous signaling and resistance to ibrutinib.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

55 Samples

Download data: CEL

(Submitter supplied) The bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors including MYC. However, only a subset of CRC cells response to BETi, suggesting an intrinsic resistance to BETi in CRC. We investigated the effect of JQ1 on cell proliferation, apoptosis, angiogenesis and MYC expression in a panel of 11 CRC cells in vitro and in vivo. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16791 GPL18573

152 Samples

Download data: BED

(Submitter supplied) Ibrutinib, a bruton's tyrosine kinase inhibitor, was shown to have high response rates in mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. However, emergence of ibrutinib resistance (IR) and subsequent fatal progression is of significant clinical concern. By implementing genomics, chemical proteomics and drug screening, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the malignant phenotype of IR. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

60 Samples

Download data: XLSX

(Submitter supplied) Ibrutinib, a bruton's tyrosine kinase inhibitor, was shown to have high response rates in mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. However, emergence of ibrutinib resistance (IR) and subsequent fatal progression is of significant clinical concern. By implementing genomics, chemical proteomics and drug screening, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the malignant phenotype of IR. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

8 Samples

Download data: BED

(Submitter supplied) Ibrutinib, a bruton's tyrosine kinase inhibitor, was shown to have high response rates in mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. However, emergence of ibrutinib resistance (IR) and subsequent fatal progression is of significant clinical concern. By implementing genomics, chemical proteomics and drug screening, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the malignant phenotype of IR. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

84 Samples

Download data: CSV

(Submitter supplied) Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin’s lymphoma, which is characterized by the translocation of t(11:14)(q13;q32) resulting in overexpression of cyclin D1. Patients with MCL often acquire resistance to conventional chemotherapy such as R-CHOP, BR, and ibrutinib. Therefore, novel therapeutic targets for relapsed MCL are needed. EZH1/2 are catalytic components of PRC2, which trimethylates H3K27 to repress transcription of target genes and play critical roles in B-cell development. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

15 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL570 GPL17586

92 Samples

Download data: CEL

(Submitter supplied) Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton’s tyrosine kinase (BTK)–mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17586

4 Samples

Download data: CEL

(Submitter supplied) Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton’s tyrosine kinase (BTK)–mediated B-cell receptor (BCR) signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

88 Samples

Download data: CEL

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone 3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using either bromodomain inhibition or CDK7 blockade. We observe that targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and that DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL20301

26 Samples

Download data: BW, TXT