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Items: 16

1.

The role of FAM46C in myeloma cells [array]

(Submitter supplied) FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis is not determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity indicating a MM survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP. more...
Organism:
Homo sapiens
Type:
Expression profiling by array
Platform:
GPL17586
3 Samples
Download data: CEL, CHP
Series
Accession:
GSE99357
ID:
200099357
2.

The role of FAM46C in myeloma cells

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing; Expression profiling by array
Platforms:
GPL11154 GPL17586
11 Samples
Download data: CEL, CHP
Series
Accession:
GSE99358
ID:
200099358
3.

The role of FAM46C in myeloma cells [sequencing]

(Submitter supplied) FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis is not determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity indicating a MM survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL11154
8 Samples
Download data: TXT
Series
Accession:
GSE99356
ID:
200099356
4.

The FAM46C gene encodes a non-canonical poly(A) polymerase and acts as an onco-suppressor in multiple myeloma

(Submitter supplied) FAM46C is one of the most frequently mutated genes in multiple myeloma (MM) and encodes a protein of unknown function. Using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active cytoplasmic non-canonical poly(A) polymerase, which enhances mRNA stability and gene expression. Moreover, we also found that the reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induced cell death. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platforms:
GPL18573 GPL11154
26 Samples
Download data: BW, TXT
Series
Accession:
GSE83772
ID:
200083772
5.

FAM46C controls antibody production by the polyadenylation of Ig mRNAs and inhibits cell migration in multiple myeloma

(Submitter supplied) FAM46C, which is frequently mutated in multiple myeloma (MM), has recently been shown to encode a non-canonical poly(A) polymerase (ncPAP). However, its target mRNAs and its role in MM pathogenesis remain largely unknown. Using CRISPR-Cas9 technology and gene expression analysis we found that inactivation of FAM46C in MM downregulates immunoglobulins (Igs) and several mRNAs encoding ER-resident proteins, including some involved in unfolded protein responses (UPRs), such as PDIA6, ERP44 and EDEM2, and others that affect glycosylation, such as SSR4, AGA and DDOST. more...
Organism:
Homo sapiens
Type:
Expression profiling by array
Platform:
GPL15207
6 Samples
Download data: CEL
Series
Accession:
GSE114984
ID:
200114984
6.

The BET bromodomain inhibitor CPI203 improves lenalidomide activity in in vitro and in vivo models of multiple myeloma by synergistic blockade of Ikaros and c-Myc signaling

(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
Series
Accession:
GSE87403
ID:
200087403
7.

Gene expression analysis of ectopic cyclin D1-expressing myeloma cells compared to their non expressing counterparts

(Submitter supplied) We analyzed gene expression profiles of myeloma cells belonging to the group of bas prognosis RPMI 8226 and LP1 expressing either the GFP protein or a cyclin D1-GFP fusion protein
Organism:
Homo sapiens
Type:
Expression profiling by array
Platform:
GPL10558
16 Samples
Download data: TXT
Series
Accession:
GSE59673
ID:
200059673
8.

Amiloride, an old diuretic drug, is a potential therapeutic agent for multiple myeloma

(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
Series
Accession:
GSE95077
ID:
200095077
9.

Gene expression profile of human multiple myeloma cell line MM.1S after knockdown of KDM6B

(Submitter supplied) Recent studies have delineated cancer type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM); and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. TNFα or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting KDM6B is regulated by NF-κB signaling in MM cells. more...
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL11154
6 Samples
Download data: TXT
Series
Accession:
GSE93395
ID:
200093395
10.

An autoregulatory RelB:p50 NF-κB pathway perpetuates pro-survival TNF response in multiple myeloma

(Submitter supplied) Pro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-κB dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-κB activity upon TNF treatment. more...
Organism:
Mus musculus
Type:
Expression profiling by array
Platform:
GPL6885
12 Samples
Download data: TXT
Series
Accession:
GSE68615
ID:
200068615
11.

UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition

(Submitter supplied) In this project we analyze the transcriptome of the human multiple myeloma isogenic cell lines ARP-1 (UTX wild-type) and ARD (UTX null). The transcriptome is studied at baseline, upon restoration of UTX levels in ARD cells for 3 and 6 days, and upon treatment of the cell lines with the EZH2 inhibitor GSK343. Moreover, we analyzed the transcriptome of a ARD resistant cell line that we generated.
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL11154
22 Samples
Download data: CSV
Series
Accession:
GSE103567
ID:
200103567
12.

Deptor transcriptionally regulates Endoplasmic Reticulum homeostasis in Multiple Myeloma cells.

(Submitter supplied) We performed a RNA-seq analysis by using mRNA from KMS27 cells transfected with siRNA Deptor or siRNA negative control.
Organism:
Homo sapiens
Type:
Expression profiling by high throughput sequencing
Platform:
GPL10999
2 Samples
Download data: TSV
Series
Accession:
GSE79820
ID:
200079820
13.

Impact of Glucocorticoids and PI3K Inhibition on Gene Expression in Myeloma

(Submitter supplied) We previously noted that combination glucocorticoids and PI3K inhibition induces synergistic cell death. To identify genes involved in myeloma cell death we examined mRNA expression in each individual treatment and in the combination. The glucocoriticoid resistant cells (MM.1RL) are used as a negative control. Gene expression is assessed using Illumina Human HT-12v4 bead chips
Organism:
Homo sapiens
Type:
Expression profiling by array
Platform:
GPL10558
24 Samples
Download data: TXT
Series
Accession:
GSE64704
ID:
200064704
14.

Identification of glucocorticoid receptor (GR) binding sites in multiple myeloma

(Submitter supplied) Purpose: The glucocorticoid receptor is widely expressed across mutliple tissues, and yet has very tissue specfic actions. This is most likely due to the tissue specific chormatin landscape which dictates GR binding. It identify GR tragets in myeloma as potential therapeutic targets, we have used ChIP-seq to identify myeloma specific GR binding sites. Methods: DNA-chromatin complexes were isolated from MM.1S (GR positive) or MM.1RL (GR negative) cells following a 2 hour treatment with either 1 micromolar dexamethasone or vehicle control. more...
Organism:
Homo sapiens
Type:
Genome binding/occupancy profiling by high throughput sequencing
Platform:
GPL11154
12 Samples
Download data: TXT
Series
Accession:
GSE63209
ID:
200063209
15.

Comparison of the gene expression profiles of carfilzomib-resistant derivatives versus parental human myeloma cell lines

(Submitter supplied) KMS-11 and KMS-34 cells were exposed to stepwise increasing concentrations of carfilzomib over a period of 18 weeks: cells adapted to growth in 4 nM carfilzomib by 4 weeks, in 6 nM in another 6 weeks and in 12 nM after a further 8 weeks. The resulting cell cultures, denoted KMS-11/Cfz and KMS-34/Cfz, respectively, retained resistance to carfilzomib even when tested after removal of selective pressure for approximately 8 weeks.
Organism:
Homo sapiens
Type:
Expression profiling by array
Dataset:
GDS5826
Platform:
GPL570
12 Samples
Download data: CEL
Series
Accession:
GSE69078
ID:
200069078
16.
Full record GDS5826

Multiple myeloma cell lines with acquired resistance to chemotherapeutic agent carfilzomib

Analysis of proteasome inhibitor carfilzomib-resistant multiple myeloma (MM) cell lines KMS-11/Cfz and KMS-34/Cfz, after 1 week of growth in the absence of carfilzomib. Results provide insight into the molecular mechanisms underlying the acquisition of proteasome inhibitor resistance in MM.
Organism:
Homo sapiens
Type:
Expression profiling by array, transformed count, 4 cell line, 2 cell type sets
Platform:
GPL570
Series:
GSE69078
12 Samples
Download data: CEL
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