GEO DataSets

(Submitter supplied) Multiple myeloma (MM) cells were treated with the BET inhibitor CPI203 alone and in combination with lenalidomide plus dexamethasone in vitro and in vivo (mouse xenograft). We used microarrays to uncover the mechanisms underlying CPI-203 activity in MM, alone and in combination with lenalidomide plus dexamethasone (combo).

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13667

12 Samples

Download data: CEL

(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) Double Hit Lymphoma (DHL) were treated with the BRD4 inhibitor 100 nM CPI203 for 6h We used microarrays to uncover the mechanisms underlying CPI203 activity in Double Hit Lymphoma (DHL)

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13667

10 Samples

Download data: CEL

(Submitter supplied) The introduction of novel therapeutic agents has considerably improved the median survival of patients with multiple myeloma (MM). However, the natural history of the disease is characterized by continuous relapses over time. As a consequence, the development of new drugs is still required to treat MM recurrence. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

18 Samples

Download data: TXT

(Submitter supplied) Epigenetic alterations play an important role in the pathogenesis in multiple myeloma (MM), but its biological and clinical relevance is not fully understood. Here, we show that DOT1L, which catalyzes methylation of histone H3 lysine 79, is required for the survival of MM cells. Treatment with DOT1L inhibitors induced cell cycle arrest and apoptosis in MM cells, and strongly suppressed cell proliferation in vitro. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16699

12 Samples

Download data: TXT

(Submitter supplied) We sequenced mRNA from 12 human cancer cell lines treated with DMSO or AZD5153 for 24h to determine compound mechanism of action

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

48 Samples

Download data: TXT

(Submitter supplied) To dissect the roles of ARID2 and Aiolos in pomalidomide-induced transcriptional changes, we performed mRNA-sequencing of MM.1S cells expressing shRNA against ARID2 or Aiolos and compared them with MM.1S cells that were treated with pomalidomide for 24, 48, or 72 hours.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

21 Samples

Download data: TXT

(Submitter supplied) MYC genes are frequently amplified and correlate with poor prognosis in MB. BET bromodomains recognize acetylated lysine residues and often promote and maintain MYC transcription. Certain cyclin-dependent kinases (CDKs) are further known to support MYC stabilization in tumor cells. In this report, MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16331 GPL17301

50 Samples

Download data: TSV

(Submitter supplied) Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1 and IKZF3 in human MM cell lines to gain further insight into their downstream gene regulatory networks. Our findings strongly support the central role of Ikaros and Aiolos in the action of the IMiDs. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

18 Samples

Download data: TXT

(Submitter supplied) Pathologic activation of c-Myc plays a central role in pathogenesis of several neoplasias, including multiple myeloma. However, therapeutic targeting of c-Myc has remained elusive due to its lack of a clear ligand-binding domain. We therefore targeted c-Myc transcriptional function by another means, namely the disruption of chromatin-dependent signal transduction. Members of the bromodomain and extra-terminal (BET) subfamily of human bromodomain proteins (BRD2, BRD3 and BRD4) associate with acetylated chromatin and facilitate transcriptional activation by increasing the effective molarity of recruited transcriptional activators. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

12 Samples

Download data: CEL

(Submitter supplied) Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

12 Samples

Download data: CSV

(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) Lenalidomide is a therapeutically active compound that binds to E3 ubiquitin ligase recruiter cereblon (CRBN) and induces cytotoxicity. We have identified eukaryotic translation initiation factor 2 subunit C2 (EIF2C2) as a new member of CRBN-downstream binding protein that plays an important role in microRNA (miRNA) maturation and function. The treatment of immunomodulatory drug (IMiD)-sensitive multiple myeloma (MM) cells with lenalidomide altered the steady-state levels of CRBN, EIF2C2 and miRNAs and induced apoptosis. more...

Organism:

Homo sapiens

Type:

Expression profiling by RT-PCR

Platform:

GPL19220

12 Samples

Download data: TXT

(Submitter supplied) BET bromodomain inhibitors are known to block prostate cancer cell survival through suppression of c-Myc and androgen receptor (AR) function. However, little is known about other transcriptional modulators whose function is blocked by these drugs and the anti-tumor activity of BET bromodomain inhibition in AR-independent castration-resistant prostate cancers (CRPC), whose frequency may be increasing. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL11154

34 Samples

Download data: BED, TXT

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

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platform:

GPL16686

36 Samples

Download data: CEL

(Submitter supplied) Kinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platform:

GPL16686

24 Samples

Download data: CEL

(Submitter supplied) Kinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

12 Samples

Download data: CEL

(Submitter supplied) Previous study demonstrated that HDAC3 has a critical role in MM proliferation; however, the underlying mechanism has not yet been elucidated. We identify that HDAC3 inhibition targets DNMT1 through dual regulations. We demonstrate that knockdown of DNMT1 leads to apoptosis and significant growth inhibition in myeloma cells. HDAC3 inhibition by gene silencing or HDAC3 selective inhibitor BG45 downregulates an oncoprotein c-Myc through its acetylation. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

10 Samples

Download data: CEL

(Submitter supplied) Recurrent chromosomal translocations are central to the pathogenesis of multiple myeloma (MM), with t(4;14) translocation being the second-most common and associated with poor prognosis. The nuclear receptor-binding SET domain 2 (NSD2) is overexpressed as a result of the translocation and has been suggested to be the primary oncogenic factor in t(4;14) MM. However, the detailed oncogenic mechanism of NSD2 in MM is still not completely understood. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

4 Samples

Download data: TXT

(Submitter supplied) Several studies demonstrate that the bromodomain inhibitor OTX015 has preclinical antitumor activity in a variety of solid tumors and hematologic cancers. However, translation of these data to molecules suitable for clinical development has not yet to be accomplished in multiple myeloma (MM). Here, we identified genes and biologic processes that underpin the antimyeloma activity of OTX015 with global transcriptomics. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL21185

6 Samples

Download data: TXT