GEO DataSets

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

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by genome tiling array

Platforms:

GPL4091 GPL570

17 Samples

Download data: CEL, TXT

(Submitter supplied) The precise molecular mechanism of action and targets through which thalidomide and related immunomodulatory drugs (IMiDs) exert their anti-tumor effects remains unclear. We investigated the role of cereblon (CRBN), a primary teratogenic target of thalidomide, in the anti-myeloma activity of IMiDs. CRBN depletion is initially cytotoxic to human myeloma cells but surviving cells with stable CRBN depletion become highly resistant to both lenalidomide and pomalidomide, but not to the unrelated drugs bortezomib, dexamethasone and melphalan. more...

Organism:

Homo sapiens

Type:

Genome variation profiling by genome tiling array

Platform:

GPL4091

2 Samples

Download data: TXT

(Submitter supplied) The precise molecular mechanism of action and targets through which thalidomide and related immunomodulatory drugs (IMiDs) exert their anti-tumor effects remains unclear. We investigated the role of cereblon (CRBN), a primary teratogenic target of thalidomide, in the anti-myeloma activity of IMiDs. CRBN depletion is initially cytotoxic to human myeloma cells but surviving cells with stable CRBN depletion become highly resistant to both lenalidomide and pomalidomide, but not to the unrelated drugs bortezomib, dexamethasone and melphalan. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

15 Samples

Download data: CEL

(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) 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) In the 1950s the drug thalidomide administered as a sedative to pregnant women led ot the birth of thousands of children with multiple defects. Despite its teratogenicity, thalidomide and ist IMiD derivatives recently emerged as effective treatments for multiple myeloma and 5q-dysplasia. IMiDs target the CUL4-RBX1-DDB1-CRBN (CRL4(CRBN)) ubiquitin ligase. Through an unbiased screen we identify the homeobox trranscription factor MEIS2 as an endogenous substrate of CRL4(CRBN).

Organism:

Homo sapiens

Type:

Protein profiling by protein array

Platform:

GPL14689

16 Samples

Download data: GPR

(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) Gene Expression profiling of 170 newly diagnosed Multiple Myeloma patients Gene Expression profiling of Multiple Myeloma

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

176 Samples

Download data: CEL

(Submitter supplied) Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL21980

4 Samples

Download data: CEL

(Submitter supplied) Thalidomide and its derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of hematologic malignancies. It was shown that IMiDs impart gain of function properties to the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) ubiquitin ligase that enable binding, ubiquitination and degradation of key therapeutic targets such as IKFZ1, IKZF3 and CSNK1A1. While these substrates have been implicated as efficacy targets in multiple myeloma (MM) and 5q deletion associated myelodysplastic syndrome (del(5q)-MDS), other targets likely exist. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

8 Samples

Download data: CSV

(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) Multiple myeloma is a genetically heterogeneous disease of plasma cells. The thalidomide analog lenalidomide is a mainstay in the treatment of multiple myeloma and is used in combination with other drugs such as corticosteroids, chemotherapy and proteasome inhibitors, achieving high remission rates. However, most patients relapse due to acquired resistance of the malignant cells. Genetic analyses have revealed mutations in CRBN, the target of all IMiDs, as a resistance mechanism in 10% of patients, while for the majority of cases, the mechanism of resistance is unknown. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

10 Samples

Download data: TXT

(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) Heterobifunctional proteolysis-targeting chimeric compounds leverage the activity of E3 ligases to induce degradation of target oncoproteins and exhibit potent preclinical antitumor activity. To dissect the mechanisms regulating tumor cell sensitivity to different classes of pharmacological "degraders" of oncoproteins, we performed genome-scale CRISPR/Cas9-based gene-editing studies. We observed that myeloma cell resistance to "degraders" of different targets (BET bromodomain proteins, CDK9) and operating through CRBN (degronimids) or VHL is primarily mediated by prevention of, rather than adaptation to, breakdown of the target oncoprotein; involves loss-of-function for the cognate E3 ligase or interactors/regulators of the respective cullin-RING ligase (CRL) complex. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

42 Samples

Download data: TXT

(Submitter supplied) Thalidomide has a dark history as a teratogen, but in recent years its derivates have been shown to function as a chemotherapeutic agent. These drugs bind cereblon (CRBN), the substrate receptor of an E3 ubiquitin ligase complex and modify its degradation targets. Despite these insights, remarkably little is known about the normal function of cereblon in development. Here we employ Ciona, an invertebrate chordate, to identify endogenous Crbn targets. more...

Organism:

Ciona intestinalis

Type:

Expression profiling by high throughput sequencing

Platform:

GPL29701

2 Samples

Download data: H5

(Submitter supplied) Adult T-cell lymphoma/leukemia (ATL) is an aggressive subtype of leukemia/lymphoma caused by human T-cell leukemia virus type-1 (HTLV-1) and existing chemotherapy for ATL remains with extremely poor prognosis. Therefore, more effective therapeutic options are urgent needs for this disease. Since recent two clinical studies proved promising curability of Lenalidomide (LEN, a second-generation immunomodulatory drug [IMiDs]) for ATL patients, we investigated the direct growth-inhibitory machineries of LEN on ATL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17077

6 Samples

Download data: TXT

(Submitter supplied) Adult T-cell lymphoma/leukemia (ATL) is an aggressive subtype of leukemia/lymphoma caused by human T-cell leukemia virus type-1 (HTLV-1) and existing chemotherapy for ATL remains with extremely poor prognosis. Therefore, more effective therapeutic options are urgent needs for this disease. Since recent two clinical studies proved promising curability of Lenalidomide (LEN, a second-generation immunomodulatory drug [IMiDs]) for ATL patients, we investigated the direct growth-inhibitory machineries of LEN on ATL cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17077

6 Samples

Download data: TXT

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

Organism:

Homo sapiens

Type:

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

Platforms:

GPL18573 GPL21290 GPL11154

44 Samples

Download data: BW

(Submitter supplied) Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiDs). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: BW