Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA125293 | ENA |
REPOSITORIES: ENA
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Project description:Multiple Myeloma primary myeloma cells of 131 patients, 10 human myeloma cell lines, bone marrow stromal cells of 5 myeloma patients, bone marrow CD3 cells of 5 myeloma patients, bone marrow CD14 cells of 5 myeloma patients, bone marrow CD15 cells of 5 myeloma patients, in vitro generated osteoclastic cells of 7 myeloma patients, 7 normal plasmablasts and 6 normal memory B cells.
2011-03-08 | E-TABM-937 | biostudies-arrayexpress
Project description:The unique properties of the bone marrow allow for migration and proliferation of multipl myeloma (MM) cells, while also providing the perfect environment for development of quiescent, drug-resistant MM cell clones. Bone marrow adipocytes (BMAds), which have recently been identified as important contributors to systemic adipokine levels, bone strength, hematopoiesis, and progression of metastatic and primary bone marrow cancers, such as MM. Recent studies in myeloma suggest that BMAds can be reprogrammed by tumor cells to contribute to myeloma-induced bone disease, and reciprocally, BMAds support MM cells in vitro. Importantly, most data investigating BMAds have been generated using adipocytes derived by differentiating bone marrow-derived mesenchymal stromal cells (MSCs) into adipocytes in vitro using adipogenic media, due to the extreme technical challenges associated with isolating and culturing primary adipocytes. However, if studies could be performed with primary adipocytes, they likely will recapitulate in vivo biology better than MSC-derived adipocyte, as the differentiation process is artificial and differs from in vivo differentiation, and progenitor cell(s) of the primary BMAd may not be the same as the MSCs precursors used for adipogenic differentiation in vitro. Therefore, we developed and refined three methods for culturing primary BMAds (pBMAds): 2D coverslips, 2D transwells, and 3D silk scaffolds, all of which can be cultured alone or with MM cells to investigate bidirectional tumor-host signaling. To develop an in vitro model with a tissue-like structure to mimic the bone marrow microenvironment, we developed the first 3D, tissue engineered model utilizing pBMAds derived from human bone marrow. We found that pBMAds, which are extremely fragile, can be isolated and stably cultured in 2D for 10 days and in 3D for short term (~2 weeks) or long term (1 month) in vitro. To investigate the relationship between pBMAds and myeloma, MM cells can be added to investigate physical relationships through confocal imaging and soluble signaling molecules via mass spectrometry. In sum, we developed three in vitro cell culture systems to study primary bone marrow adipocytes and myeloma cells, which could be adapted to investigate many diseases and biological processes involving the bone marrow, including other bone-homing tumor types.
2023-01-04 | PXD032753 | Pride
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
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
Project description:The gene expression profiles of human bone marrow stromal cells
| PRJNA312974 | ENA
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.
2016-08-20 | GSE85837 | GEO
Project description:The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.
2024-04-04 | GSE263178 | GEO
Project description:Gene expression analysis of bone marrow stromal cells from multiple myeloma patients and controls
| PRJNA339521 | ENA
Project description:Comparison of bone-marrow mesenchymal stromal cells from multiple myeloma patients and healthy donors
| PRJNA153503 | ENA
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