Primary bone marrow stromal cells in plasma cell disorders
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ABSTRACT:
PROVIDER: PRJNA532852 | ENA |
REPOSITORIES: ENA
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Project description:Multiple myeloma (MM) and its premalignant precursor MGUS (monoclonal gammopathy of undetermined significance) are clonal plasma cell diseases that develop in the bone marrow (BM) and are dependent on microenvironmental interactions. Primary bone marrow stromal cells (BMSCs) are key players in the BM microenvironment, however, their role in MGUS/MM pathophysiology is not known. We therefore investigated potential disease-specific alterations in prospectively isolated BMSCs from MM, MGUS and healthy controls. Clear disease-related BMSC surface marker and gene expression differences were recorded, and deep sequencing identified shared MGUS/MM as well as MM-specific molecular signatures. Moreover, we identified genes that were deregulated in a disease-stage manner, thus reflecting the progression from normal to MGUS and MM. Analysis of primary BMSCs revealed disease-stage related protein and gene expression patterns, which provides novel insight into the stromal transitions and their functional implications for plasma cell disease development and progression.
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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: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.
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Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironment. Within these niches, Mesenchymal Stromal Cells (BM-MSC) play a supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic progenitors. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic progenitor deregulation that features PMF. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders Transcriptome analysis was performed on BM-MSC amplified in vitro after 3 to 5 passages. Agilent Whole Human Genome Oligo Microarrays were used to compare expression profiling of BM-MSC from PMF patients and healthy donors.
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Project description:In order to comprehensively characterize bone marrow mesenchymal cells after myeloablation, single-nuclei RNA sequencing was performed on bone marrow adipocytes and bone marrow stromal cells isolated from sublethally-irradiated mice.
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