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

ABSTRACT: 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(S): Homo sapiens

PROVIDER: GSE69078 | GEO | 2015/07/09

SECONDARY ACCESSION(S): PRJNA284490

REPOSITORIES: GEO

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

Project description: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. KMS-11/Cfz and KMS-34/Cfz cells were profiled for gene expression after 1 week of growth in the absence of carfilzomib together with parental KMS-11 and KMS-34 cells which had not been selected in the drug (triplicate samples).

2015-07-09 | E-GEOD-69078 | biostudies-arrayexpress

Comparative expression analysis of carfilzomib-resistant and parental LP-1 human multiple myeloma cells

Project description:LP-1 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 culture, denoted LP-1/Cfz, retained resistance to carfilzomib even when tested after removal of selective pressure for approximately 8 weeks.

2016-09-13 | GSE78069 | GEO

PolyA RNA-seq from liposarcoma cells treated with Nutlin3R and/or Carfilzomib

Project description:Analysis of steady-state mRNA levels in liposarcoma cells treated for 28 hr with 0.05% DMSO or 10 uM Nutlin3R and/or 12.5 nM Carfilzomib

2023-05-12 | GSE226530 | GEO

Single cell RNA sequencing of murine hearts after acute proteasome inhibition

Project description:Bortezomib (BTZ), Carfilzomib (CFZ) and Ixazomib (IXA) are proteasome inhibitors (PI) approved for Multiple Myeloma (MM) treatment. By design, they all target the rate-limiting proteasome beta 5 (B5) subunit. CFZ treatment increases the survival of patients with relapsed/refractory MM compared to BTZ but is associated with heart failure not commonly observed for BTZ. The molecular basis for CFZ-induced cardiotoxicity is poorly understood. We time to investigate the transcriptomic effects of acute proteasome inhibition in the murine heart.

2023-07-01 | E-MTAB-11028 | biostudies-arrayexpress

miRNA expression of myeloma cell lines cultured with HDAC inhibitors panobinostat and vorinostat

Project description:miRNA expression of myeloma cell lines (MM.1S and KMS-11) cultured with HDAC inhibitors (10 nM panobinostat and 1 uM vorinostat) for 48h.

2024-01-31 | GSE253488 | GEO

Expression data from DMSO- and ATRA-treated human multiple myeloma (MM) cells

Project description:All-trans retinoic acid (ATRA) is important for sensitizing MM cells to carfilzomib (Cfz). To determine what signalling pathways are affected by ATRA in Cfz-treated MM cells, MM.1S MM cell line was pulsed with Cfz and then cultured with DMSO or 10µM ATRA for 12 h. Total RNAs of 2 x 106 MM.1S cells were extracted by RNeasy Mini Kit (Qiagen). 5-10 µg RNA samples were sent to Gene Expression and Genotyping Facility at Case Western Reserve University (Cleveland, OH) for genearray followed by data analysis. We use microarray data to determine differential expression of genes in Cfz-treated MM cells in culture with DMSO and ATRA.

2021-01-01 | GSE153196 | GEO

Global gene expression profiles of cellular response in human induced pluripotent stem cell-derived cardiomyocytes to CFZ treatment

Project description:Purpose: Evaluate the molecular changes associated with Cfz -induced cardiotoxicity Methods: RNA-Seq analysis was performed to analyze global transcriptome profiles of hiPSC-CMs treated with DMSO (Control group), 1 µM Carfilzomib ( Cfz group). The Illumina TruSeq technology was used to prepare RNA-Seq libraries, and next-generation sequencing was done via an Illumina HiSeq 2000. RNA sequence reads were aligned to the human reference genome (GRCh38) using STAR v2.5. HTSeq v0.6.1 was used to count the read numbers mapped of each gene, and then Fragments Per Kilobase Million (FPKM) was calculated to estimate gene abundance. Differential expression analysis was performed using the DESeq2 R package (2_1.6.3). The resulting P-values were adjusted using the Benjamini and Hochberg's approach. As detected by RNA-Seq, some differential genes regulated by Cfz were significantly involved in cardiac contraction and extracellular matrix (ECM). Among the top 10 up-regulated genes post Cfz treatment,most of thoese genes was related to the heat shock protein expression( HSPA1B,HSPA6,,HSPH1, BAG3). And among the top 10 down-regulated genes post Cfz treatment, some correlated to contraction and Extra cellular matrix ( ITG11, SLC9A3, TNN1) . Conclusion: Carfilzomib -induced alteration of hiPSC-CM transcriptomic profiles. Enhanced HSPs and down regulate cardiac related contraction gene and extracellular matrix.

2021-10-04 | GSE163102 | GEO

Secondary proteasome inhibitor carfilzomib resistant myeloma cell lines

Project description:Modulation of the activity of the ubiquitin-proteasome pathway with the proteasome inhibitor (PI) is an established component of therapy for plasma cell disorders. However, resistance emerges and the mechanism is incompletely understood. We generated carfilzomib-resistant (CR) myeloma cell lines by exposing drug-naive ANBL-6, KAS-6/1, U266, and OPM-2 cells to increasing concentrations of carfilzomib and then performed gene expression profiling (GEP) to identify prominent changes compared to their vehicle-treated counterparts, followed by exploration of the mechanism(s) of proteasome inhibitor resistance.

2016-10-09 | GSE62237 | GEO

Dynamics of intercellular and exosomal miRNAs in hypoxia-resistant KMS-11 cells

Project description:In multiple myeloma (MM), abnormal plasma cells interact with bone marrow (BM) stromal cells and vascular cells among others. A part of the BM milieu is considered highly hypoxic, and myeloma cells in situ may be influenced by circumstances other than normoxia in vitro. Hence, we attempted to confirm the role of hypoxic MM-derived exosomes in the BM milieu. We established a novel hypoxia-resistant cell line, KMS-11-HR, derived from KMS-11 cells cultured for >4 months under hypoxia (1% O2), as a model of MM cells localizing in an extensively hypoxic milieu. We used KMS-11 cells and KMS-11-HR cells, as donor cells, and HUVECs as recipient cells. Exosomes derived from KMS-11 cells (normoxia or hypoxia) and exosomes derived from KMS-11-HR cells (hypoxia-resistant sub-line) were used for validation of angiogeneic activity, such as tube formation assay. Exosomes derived from the KMS-11-HR cells significantly increased tube formation of HUVECs than those from KMS-11 cells. To identify intercellular and exosomal miRNAs specifically expressed in hypoxia-resistant cells, we assess the expression profiles of intercellular and extracellular miRNAs in KMS-11 cells and KMS-11-HR cells using Taqman MicroRNA Array v2.0 (Applied Biosystems, Bedford, MA).

2014-10-15 | GSE48908 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of transcriptomes in MM.1S cells treated with DMSO, All-trans retinoic acid (ATRA), carfilzomib (Cfz), and their combinations

Project description:ATRA is important for sensitizing MM cells to Cfz. To determine what signalling pathways are affected by ATRA+Cfz in MM cells, MM.1S MM cell line was pulsed with Cfz and then cultured with DMSO or 10µM ATRA for 12 h. Total RNAs of 2 x 106 MM.1S cells for each sample were extracted by RNeasy Mini Kit (Qiagen). 5-10 µg RNA samples were sent to Cancer Genomics Center at The University of Texas (Houston, TX) for genearray followed by data analysis. We use gene experssion profiling data to determine differential expression of genes in MM cells in culture with DMSO, ATRA, Cfz or ATRA+Cfz.

2021-12-31 | GSE178340 | GEO

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