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Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

ABSTRACT: Multiple myeloma RPMI8226 cells adapted to growth in melphalan display a shift towards Warburg metabolism and modulated oxidative stress signaling Inhibitors targeting specific enzymes in these pathways are selectively toxic to the melphalan-resistant cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60970 | GEO | 2014/09/03

SECONDARY ACCESSION(S): PRJNA260009

REPOSITORIES: GEO

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Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

Project description:Multiple myeloma RPMI8226 cells adapted to growth in melphalan display a shift towards Warburg metabolism and modulated oxidative stress signaling. Inhibitors targeting specific enzymes in these pathways are selectively toxic to the melphalan-resistant cells. To investigate large scale alterations in gene expression accompanying melphalan resistance, we used the multiple myeloma cell line RPMI8226 and its melphalan-resistant derivative LR5. The stable isotope labeling by amino acids in cell culture (SILAC) approach.

2015-05-26 | PXD001276 | Pride

Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

Project description:Multiple myeloma RPMI8226 cells adapted to growth in melphalan display a shift towards Warburg metabolism and modulated oxidative stress signaling Inhibitors targeting specific enzymes in these pathways are selectively toxic to the melphalan-resistant cells. The gene expression profiles were measured on 6 batches each of control and melphalan-treated RPMI8226 and RPMI8226-LR5 cells using Illumina Human HT-12 v3 Expression BeadChip (Illumina, San Diego, CA), which enables genome-wide expression analysis (more than 47 000 transcripts) of 24 samples in parallel on a single microarray.

2014-09-03 | E-GEOD-60970 | biostudies-arrayexpress

Metabolic Changes Contribute to Melphalan Resistance in Multiple Myeloma

Project description:Multiple myeloma is an incurable hematological malignancy that impacts tens of thousands of people every year in the U.S. Treatment for eligible patients includes three stages: induction, consolidation with stem cell rescue, and maintenance. High dose therapy with the DNA alkylating agent, melphalan, remains the primary drug for consolidation therapy in conjunction with autologous stem cell transplant. As a result, melphalan resistance remains a clinical challenge. Here, we use proteometabolomics to examine mechanisms of melphalan resistance in two cell line models. Drug metabolism, steady-state metabolomics, activity-based protein profiling (ABPP), acute treatment metabolomics, and immunoblotting analyses have allowed us to further elucidate metabolic processes contributing to melphalan resistance. Proteometabolomics data indicate that both drug resistant cells have higher levels of pentose phosphate pathway metabolites than their naïve counterparts. Interestingly, we also observed cell line specific changes in purine, pyrimidine and glutathione metabolism that are linked to the differences in steady state metabolism of naïve cells and highlight the heterogeneity of melphalan resistance in these models. Because of the diversity of metabolic changes, our data suggest that omics approaches will be needed to fully examine melphalan resistance in patient specimens and define personalized strategies to optimize the delivery of this therapy.

2020-07-17 | PXD019725 | Pride

Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells.

Project description: Not available

| S-EPMC4358942 | biostudies-literature

Drug resistance-related changes in gene expression profile in multiple myeloma

Project description:1) We identified the genes whose expression was up- and down-regulated by the adhesion to bone marrow stromal cells in human multiple myeloma cell line RPMI8226. 2) We identified the genes whose expression was up- and down-regulated by the PI3K inhibitor PF-04691502 in human multiple myeloma cell line RPMI8226. We isolated mRNA from the multiple myeloma cell line RPMI8226 under drug-resistant conditions, and subjected them to gene expression profiling using an Agilent GeneChip Array.

2015-03-04 | E-GEOD-66466 | biostudies-arrayexpress

DNA methylation data from cell lines originating from patients with multiple myeloma

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2015-06-30 | E-GEOD-68259 | biostudies-arrayexpress

Illumina Infinium whole-genome SNP-CN data from cell lines originating from patients with multiple myeloma

Project description:We performed Illumina Infinium whole-genome SNP-CN profiling of KMS11, MM.1S, and RPMI8226 multiple myeloma cell lines to detect gene copy number variants distinct to each cell line Three multiple myeloma cell lines (KMS11, MM.1S, and RPMI8226)

2015-06-30 | E-GEOD-68258 | biostudies-arrayexpress

Drug resistance-related changes in gene expression profile in multiple myeloma

2015-03-04 | GSE66466 | GEO

Tak1-inhibitors are cytotoxic for multiple myeloma cells alone and in combination with melphalan

Project description:To determine which genes are affected by NG25 and melphalan, we performed an RNA-seq on INA-6 cells treated with NG25, melphalan or a combination of the two. GSEA focusing on the hallmark pathways showed that melphalan-treatment upregulated genes involved in UV-response, DNA-repair, p53-pathway and TNF-signaling via NF-kB. NG25 induced expression of genes involved in cholesterol homeostasis and mTORC1-signaling and down-regulated MYC- and E2F-targets. MYC is a central driver of MM pathology, and regulate survival as well as cell cycle control through E2F. NG25 reversed the melphalan-induced UV-response.

2021-06-17 | GSE178292 | GEO

Protective effects on melphalan-induced mouse intestinal injury treated by Human Umbilical Cord-derived Mesenchymal Stem Cells

Project description:Autologous peripheral hematopoietic stem cell transplantation (autoHSCT) is one front-line therapy with high-dose melphalan for multiple myeloma (MM). Patients with MM who receive conditioning regimen with melphalan usually suffer from severe gastrointestinal symptoms, as one of nonhematological toxicities. Aim: It is an urgent demand to develop an effective methods to repair the intestinal injuries in patients with MM receiving conditioning regimen with high-dose melphalan for autoHSCT. Therefore, the protective effects of Human umbilical cord derived-mesenchymal stem cells (hucMSCs) is investigated after infusion into mouse model with melphalan-induce gastrointestinal injuries.

2024-04-01 | GSE225899 | GEO

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