Genome-wide profiling of endothelial progenitor cells in multiple myeloma: disease-relevant pathways and genomic markers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE28331 | GEO | 2011/04/02
SECONDARY ACCESSION(S): PRJNA139477
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-04-02 | E-GEOD-28331 | biostudies-arrayexpress
Project description:BackgroundIn multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization.MethodsA total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH).ResultsIn 11 patients, analysis of EPCs by HUMARA revealed significant skewing (> or = 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (> or = 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI.ConclusionOur results suggest that EPCs in at least a substantial subpopulation of MM patients are related to the neoplastic clone and that this is an important mechanism for upregulation of tumor neovascularization in MM.
| S-EPMC1557670 | biostudies-literature
Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. EPCs from 20 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression. EPCs 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-28326 | biostudies-arrayexpress
Project description:In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication.
| S-EPMC6286326 | biostudies-other
Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. EPCs from 20 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression.
2011-04-02 | GSE28326 | GEO
Project description:In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication.
| S-EPMC6092251 | biostudies-literature
Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. EPCs from 16 newly diagnosed patients with advanced MM were examined for genomic instability by aCGH to assess chromosomal gains and losses. Data were compared to aCGH results from corresponding CD138+ tumor plasma cells from these patients. EPCs and tumor cells were derived from single-cell suspensions of bone marrow (BM) aspirates from newly diagnosed MM patients, and total genomic DNA was extracted for aCGH. DNA from healthy male peripheral blood mononuclear cells (PBMCs; Promega, Madison, WI) was used as the normal control DNA.
2011-04-02 | E-GEOD-28329 | biostudies-arrayexpress
Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. EPCs from 16 newly diagnosed patients with advanced MM were examined for genomic instability by aCGH to assess chromosomal gains and losses. Data were compared to aCGH results from corresponding CD138+ tumor plasma cells from these patients.
2011-04-02 | GSE28329 | GEO
Project description:Multiple Myeloma Genomic Study (MMGS)
| PRJNA377962 | ENA
Project description:Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies.
| S-EPMC3727863 | biostudies-other