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Expression data from cell lines originating from patients with multiple myeloma, plasmacytoma and diffuse large B-cell lymphoma

ABSTRACT: A predictive gene list for response to high dose melphalan therapy in patients diagnosed with multiple myeloma is generated by combining results from dose response experiments and microarray data using a B-cell line panel and the introduction of multivariate regression techniques.

ORGANISM(S): Homo sapiens

PROVIDER: GSE22759 | GEO | 2011/04/30

SECONDARY ACCESSION(S): PRJNA128271

REPOSITORIES: GEO

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Expression data from cell lines originating from patients with multiple myeloma, plasmacytoma and diffuse large B-cell lymphoma

Project description:A predictive gene list for response to high dose melphalan therapy in patients diagnosed with multiple myeloma is generated by combining results from dose response experiments and microarray data using a B-cell line panel and the introduction of multivariate regression techniques. 18 malignant B-cell lines were analyzed by gene expression microarrays and screened for melphalan median dose dependent growth inhibition. Results are used to build a predictive gene list for response to high dose melphalan therapy in multiple myeloma.

2011-04-30 | E-GEOD-22759 | 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: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

Gene expression profiles of patients with multiple myeloma who have been treated previously

Project description:This Series represents the gene expression profiles of patients with multiple myeloma who have been treated previously. In brief, Total Therapy 6 (TT6) is an open label phase 2 protocol for patients with symptomatic multiple myeloma, who had been treated with more than one cycle of prior therapy excluding autologous hematopoietic stem cell transplant. This protocol was approved by the institutional review board on March 25, 2009 (IRB#108053). The TT6 treatment regimen consists of induction therapy with Melphalan/Bortezomib/Thalidomide/Dexamethasone/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (M-VTD-PACE) followed by a high dose M-VTD-PACE based tandem transplant. Maintenance therapy consists of Bortezomib/Lenalidomide/Dexamethasone alternating with Borteomib/Melphalan/Dexamethasone every months for 3 years.

2015-01-20 | GSE57317 | GEO

Gene expression profiles of patients with multiple myeloma who have been treated previously

2015-01-20 | E-GEOD-57317 | biostudies-arrayexpress

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

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

2014-09-03 | GSE60970 | GEO

RNA immunoprecipitation and sequencing of ILF2-bound transcripts in Multiple Myeloma

Project description:To understand the mechanistic basis of ILF2’s regulation of mRNA splicing in response to DNA damage in Multiple Myeloma, we performed RNA immunoprecipitation (RIP) and sequencing of ILF2-bound transcripts under both physiological and DNA damage (melphalan treatment) conditions. Cells were treated with melphalan for 10 hours. RNA immunopreciptation (RIP) and sequencing of ILF2-bound RNAs was performed in the JJN3 and H929 cell lines (two biological replicates/condition). Cells were treated with melphalan for 10 hours.

2017-05-23 | GSE83662 | GEO

RNA immunoprecipitation and sequencing of YB-1-bound transcripts in Multiple Myeloma

Project description:To understand the mechanistic basis of YB-1’s regulation of mRNA splicing in response to DNA damage in Multiple Myeloma, we performed RNA immunoprecipitation (RIP) and sequencing of ILF2-bound transcripts under both physiological and DNA damage (melphalan treatment) conditions. Cells were treated with melphalan for 10 hours. (RIP) and sequencing of YB-1-bound RNAs was performed in the JJN3 line (two biological replicates/condition).

2017-05-23 | GSE83664 | GEO

An IL-1β driven neutrophil-stromal cell axis fosters a BAFF-rich microenvironment in multiple myeloma

Project description:Neutrophils are the most abundant nucleated cell type in the bone marrow. A pro-tumor bias in this cell type may have implications for bone-marrow residing malignancies, such as multiple myeloma. Here, we generated single cell transcriptomic overviews of the entire myeloid compartment, including the entire neutrophilic lineage, of the bone marrow of 6 newly diagnosed myeloma patients, 5 treated myeloma patients and 4 non-cancer controls. We find dat mature neutrophils in myeloma patients, both newly diagnosed and treated, have an activated and pro-inflammatory phenotype, accompanied by increased transcription of pro-inflammatory cytokines, such as IL-1β, and myeloma cell survival factors, such as BCMA-ligand BAFF/TNFSF13B. Moreover, inflammatory stromal cells can activate naive neutrophils to acquire an inflammatory phenotype as is seen in patients. Previously, we have shown that inflammatory stromal cells characterized the bone marrow of newly diagnosed myeloma patients. Here, we generate single cell RNA sequencing dataset of non-hematopoietic bone marrow cells of patients after induction treatment, high-dose melphalan, stem cell transplantation and consolidation treatment. We show that this intensive treatment reduced, but did not normalize, stromal inflammation.

2023-03-31 | E-MTAB-12760 | biostudies-arrayexpress

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