GEO DataSets

(Submitter supplied) Knowledge of essential oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells bearing an oncogenic mutation while sparing normal cells. Lenalidomide is emerging as an active agent in diffuse large B cell lymphoma (DLBCL), especially for the activated B cell-like (ABC) subtype, but the mechanism of its action is unknown. Here we show that lenalidomide kills ABC DLBCL cells by augmenting the production of interferon 3/4, which these cells are predisposed to produce by their oncogenic MYD88 mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

8 Samples

Download data: TXT

(Submitter supplied) RNA interference screens identified the transcription factor IRF4 as essential for the survival of the activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Analysis of IRF4 genomic targets in ABC-DLBCL and Multiple Myeloma (MM) revealed that IRF4 regulates distinct networks in these cancers. IRF4 peaks in ABC-DLBCL, but not MM, were enriched for a composite ETS-IRF DNA motif that can be bound by heterodimers of IRF4 and the ETS-family transcription factor SPIB, whose expression is also essential for ABC-DLBCL survival. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

32 Samples

Download data: TXT

(Submitter supplied) Cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex CRL4CRBN, is the target of the immunomodulatory drugs lenalidomide and pomalidomide. Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of two common substrates, transcription factors Aiolos and Ikaros. Here we report that the pleiotropic pathway modifier CC-122, a new chemical entity termed pleiotropic pathway modifier binds CRBN and promotes degradation of Aiolos and Ikaros in diffuse large B-cell lymphoma (DLBCL) and T cells in vitro, in vivo and in patients, resulting in both cell autonomous as well as immunostimulatory effects. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

10 Samples

Download data: IDAT, TXT

(Submitter supplied) Chronic active B cell receptor (BCR) signaling, a hallmark of the ABC subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activates IkappaB kinase (IKK) and the classical NF-kappaB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-kappaB activity in ABC DLBCL. more...

Organism:

Homo sapiens

Type:

Genome variation profiling by SNP array

Platform:

GPL6801

5 Samples

Download data

(Submitter supplied) Chronic active B cell receptor (BCR) signaling, a hallmark of the ABC subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activates IkappaB kinase (IKK) and the classical NF-kappaB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-kappaB activity in ABC DLBCL. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL16699 GPL13607

20 Samples

Download data: TXT

(Submitter supplied) By genome-wide ChIP-seq analysis in ABC DLBCL cell lines, we identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation and migration. Whole transcriptome profiling revealed that STAT3 acts as both a transcriptional activator and suppressor.

Organism:

Homo sapiens

Type:

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

Platform:

GPL11154

10 Samples

Download data: BW, TXT

(Submitter supplied) B cell receptor (BCR) signaling has emerged as a therapeutic target in B cell lymphomas, but the precise deployment of inhibitors to target oncogenic BCR signaling requires detailed knowledge of the signaling cascades that the BCR triggers in individual tumors. Here, we have used CRISPR-Cas9 screens to investigate whether the ABC and GCB molecular subtypes of diffuse large B cell lymphoma (DLBCL) utilize distinct BCR signaling modes to sustain their proliferation and survival. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

8 Samples

Download data: TXT

(Submitter supplied) ChIP-seq data for the transcription factors (TFs) IRF4, PU.1 and SPIB from the cell lines OCI-LY3, OCI-LY10 and H929, and BATF from the cell lines OCI-Ly3 and OCI-Ly10. In addition ChIP-seq for the TFs IRF4, PU.1 and SPIB from the cell line OCI-LY3 following transfections of scramble/SPIB-siRNA.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL9115 GPL16791

22 Samples

Download data: BED, BW

(Submitter supplied) Gene expression from OCI-LY3 cells 48hrs after knock down of SPIB.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

4 Samples

Download data: TXT

(Submitter supplied) Gene expression profiling of B-cells from a model differentiation series: from Naïve B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

21 Samples

Download data: TXT

(Submitter supplied) Gene expression profiling was carried out for RNA extracted from Formalin-fixed, paraffin embedded (FFPE) biopsies for 172 patients with diffuse large b-cell lymphoma (DLBCL) using the Illumina DASL platform. Classification into GCB, ABC or Type-III subtypes was carried out revealing a significant relationship between subtype and survival.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL8432

249 Samples

Download data: TXT

(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:

GPL16699 GPL4133

12 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) To determine gene expression of DLBCL upon NF-kB inhibition or knockdown of BCR signaling components.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

24 Samples

Download data: TXT

(Submitter supplied) The ABC subtype of diffuse large B cell lymphoma (DLBCL) remains the least curable form of this lymphoma despite recent advances in therapy. We have combined structural and functional genomics to triangulate on new oncogenic mechanisms and devise new therapeutic strategies. RNA interference screen revealed a dependence of ABC DLBCL cell lines on MYD88 and IRAK1. High throughput resequencing of RNA (RNA-Seq) revealed frequent somatic mutations in MYD88 that preferentially occurred in the ABC DLBCL subtype. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

16 Samples

Download data: TXT

(Submitter supplied) Technical replicates from BC3 and BCBL1 cell lines were treated with DMSO or 5 micromoles of lenalidomide for 24 hours. NOTE: Detection p-values were neither computed nor used in this experiment. All data was processed directly from IDATs and the proportion of present probes estimated from the negative and positive controls.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

8 Samples

Download data: IDAT, TXT

(Submitter supplied) Activated B-cell-like (ABC) and germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) represent the two major molecular DLBCL subtypes. They are characterized by differences in clinical course and by divergent addiction to oncogenic pathways. To determine activity of novel compounds in these two subtypes, we conducted an unbiased pharmacologic in vitro screen. The phosphatidylinositol-3-kinase (PI3K) alpha/delta (PI3Ka/d) inhibitor AZD8835 showed marked potency in ABC DLBCL models, whereas the protein kinase B (AKT) inhibitor AZD5363 induced apoptosis in PTEN-deficient DLBCLs. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

40 Samples

Download data: TXT

(Submitter supplied) The goal of this study is to screen the differential genes between original and RCHO-resistant NU-DUL-1 cells, then analyze the significant pathways.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17303

4 Samples

Download data