GEO DataSets

(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

(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

(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

(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

(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

(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) 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

(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) 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

(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

(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

(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

(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

(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

(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

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