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Gene expression analysis of bone marrow stromal cells from multiple myeloma patients and controls

ABSTRACT: Multiple myeloma is hematologic malignancies result from clonal proliferation of plasma cells. Recently, increasing evidence supports the hypothesis that microenvironment cells play important roles in the proliferation, survival, and drug resistance of clonal plasma cells. The aim of this study is to culture stromal cells from bone marrow aspirates of patients with multiple myeloma, and to investigate expression profiles of bone marrow stromal cells and their relationships with the clinical characteristics of patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85837 | GEO | 2016/08/20

SECONDARY ACCESSION(S): PRJNA339521

REPOSITORIES: GEO

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Gene expression analysis of bone marrow stromal cells from multiple myeloma patients and controls

Project description:Multiple myeloma is hematologic malignancies result from clonal proliferation of plasma cells. Recently, increasing evidence supports the hypothesis that microenvironment cells play important roles in the proliferation, survival, and drug resistance of clonal plasma cells. The aim of this study is to culture stromal cells from bone marrow aspirates of patients with multiple myeloma, and to investigate expression profiles of bone marrow stromal cells and their relationships with the clinical characteristics of patients. RNA was extracted cultured bone marrow stromal cells from 15 patients with plasma cell neoplasms, and bone marrow stromal cells from 13 control patients with 9 B-cell lymphoma patients with no evidence of BM involvement and 4 patients with mild-to-moderate cytopenia without evidence of hematologic malignancies

2016-08-20 | E-GEOD-85837 | biostudies-arrayexpress

Hypoxia-Induced Regulation of the Proteome in Multiple Myeloma Cell Lines

Project description:Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1-6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the global proteome in MM cells and the stromal cell line HS-5 to reveal hypoxia-dependent regulation of proteins.

2022-02-16 | PXD030239 | Pride

Transcription profiling of human newly diagnised multiple myeloma patients prior to treatment

2008-06-13 | E-GEOD-4452 | biostudies-arrayexpress

Transcription profiling of human multiple myeloma aspirates (n=414) before treatment

2008-06-13 | E-GEOD-4581 | biostudies-arrayexpress

Serum protein N-glycosylation changes in multiple myeloma

Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>

2022-04-27 | MTBLS676 | MetaboLights

Transcription profiling of human bone marrow aspirate plasma cells from healthy Donors (N=22), MGUS (N=44), and Smoldering Myeloma (N=12)

Project description:This series represents bone marrow aspirates from smoldering multiple myeloma patients Experiment Overall Design: We analyzed arrays for plasma cells from 22 cases of healthy donors, 44 cases of MGUS, and 12 cases of smoldering myeloma

2008-06-14 | E-GEOD-5900 | biostudies-arrayexpress

Transcription profiling of human plasma cell samples from multiple myeloma patients before treatment

Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of newly diagnosed multiple myeloma patients susequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Baseline gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation

2008-04-07 | E-GEOD-4204 | biostudies-arrayexpress

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment

Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.

2018-10-24 | PXD006581 | Pride

Transcription profiling of human plasma cell samples from multiple myeloma patients

Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients. Experiment Overall Design: Samples in this series are: Experiment Overall Design: 1. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with high dose therapy and stem cell transplants termed Total Therapy 2 (pre-treatment TT2) Experiment Overall Design: 2. CD-138-selected plasma cells from bone marrow of patients with newly diagnosed multiple myeloma subsequently treated with Total Therapy 3 (pre treatment TT3). Experiment Overall Design: Overall Design: Experiment Overall Design: Gene expression signatures were used to: 1) develop unsupervised hierarchical cluster classes; 2) establish links with outcome following stem cell transplantation

2008-06-13 | E-GEOD-2658 | biostudies-arrayexpress

Genome-wide profiling of tumor cells in multiple myeloma

Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. They share a common bone marrow microenvironment with myeloma tumor cells. CD138+ tumor plasma cells from 12 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression. Tumor cells were derived from single-cell suspensions of bone marrow (BM) aspirates from newly diagnosed MM patients, and RNA was extracted for microarray hybridization.

2011-04-02 | E-GEOD-28327 | biostudies-arrayexpress

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