Transcriptomic analysis of Multiple Myeloma bone marrow microenvironment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE104171 | GEO | 2019/01/01
REPOSITORIES: GEO
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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
Project description:One of the hallmarks of multiple myeloma (MM) is a permissive BM microenvironment. Increasing evidence suggest that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line - MOPC315.BM -, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as Granzyme b and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.
2022-07-05 | PXD032934 | Pride
Project description:Although the "seed and soil" hypothesis was proposed by Stephen Paget at the end of the 19th century, where he said that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Thus, studies aiming a better understanding of the pathophysiology of the disease, as well as searching for new therapeutic targets are necessary and welcome. Therefore, the present study aimed to evaluate the protein expression profiling of mononuclear cells derived from BM of MM patients in comparison with these same cell types derived from healthy individuals, in order to fill this gap in MM treatment. Proteomic analysis was performed using the mass spectrometry technique and further analyses were done using bioinformatics tools, to identify dysregulated biological pathways and/or processes in the BM microenvironment of patients with MM as a result of the disease. Among the pathways identified in this study, we can highlight an upregulation of proteins related to protein biosynthesis, especially chaperone proteins, in patients with MM. Additionally, we also found an upregulation of several proteins involved in energy metabolism, which is one of the cancer hallmarks. Finally, with regard to the downregulated proteins, we can highlight mainly those involved in different pathways of the immune response, corroborating the data that has demonstrated that the immune system of MM is impaired and, therefore, the immunotherapies that have been studied recently for the treatment of the disease are extremely necessary in the search for a control and a cure for these patients who live with the disease.
2021-04-14 | PXD019126 | Pride
Project description:The multiple myeloma (MM) data set (endpoints F, G, H, and I) was contributed by the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences (UAMS, Little Rock, AR, USA). Gene expression profiling of highly purified bone marrow plasma cells was performed in newly diagnosed patients with MM. The training set consisted of 340 cases enrolled on total therapy 2 (TT2) and the validation set comprised 214 patients enrolled in total therapy 3 (TT3). Plasma cells were enriched by anti-CD138 immunomagnetic bead selection of mononuclear cell fractions of bone marrow aspirates in a central laboratory. All samples applied to the microarray contained more than 85% plasma cells as determined by 2-color flow cytometry (CD38+ and CD45-/dim) performed after selection. Dichotomized overall survival (OS) and eventfree survival (EFS) were determined based on a two-year milestone cutoff. A gene expression model of high-risk multiple myeloma was developed and validated by the data provider and later on validated in three additional independent data sets.
2010-09-11 | GSE24080 | GEO
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 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:Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described more than 30 years ago, the phenotype of MM-CSC is still a matter of debate, especially with respect to the expression of syndecan- 1 (CD138). Here, we demonstrate the presence of two subpopulations - CD138++ (95-99%) and CD138low (1-5%) - in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 surface expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are also phenotypically interconvertible. Overall, our results differ from previously published data which attribute a B-cell phenotype to MM-CSC and urge the need to explore more reliable markers to discriminate true clonogenic myeloma cells. To compare the gene expression profile of the subpopulations CD138++ and CD138low within the MM cell line, RPMI-8226. RNA was isolated from CD138++ (n=3) and CD138low (n=3) RPMI-8226 cells. RNA was hybridized to Human Gene 1.0 ST array (Affymetrix) according to Affymetrix protocols [Gutierrez, 2005, 402]. Microarray data were normalized using the Robust Multichip Analysis (RMA) algorithm implemented in the Affymetrix Expression Console. Data analysis was carried out using DNA-Chip Analyzer software (DChip). The comparison criteria used in DChip analysis were fold change E/BM-bM-^IM-%2 or B/EM-bM-^IM-%2, mean difference E-B>100 or B-E>100 and the lower 90% confidence bound of fold-change was used
2014-05-19 | E-GEOD-49482 | biostudies-arrayexpress
Project description:Gene expression analysis of CD138-depleted bone marrow cells from patients with SMM, patients with monoclonal gammopathy of undetermined significance (MGUS) and patients with symptomatic MM was performed by using Nanostring Technology
2021-12-15 | GSE186537 | GEO
Project description:Multiple myeloma (MM) is a highly refractory hematological cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which are previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA-sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA-sequencing reiterated top candidates, further affirming the ability of single cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy.
2023-01-17 | GSE223060 | GEO
Project description:Multiple myeloma (MM) is a plasma cell malignancy characterized by the presence of multiple foci in the skeleton. These distinct tumor foci indicate cycles of tumor growth and dissemination that seed new clusters and drives disease progression. Utilizing an intra-tibial Vk*MYC murine myeloma, we found that CD169 + radiation-resistant, tissue-resident macrophages (MPs) were critical for myeloma early dissemination and disease progression. While depletion of these MPs had no effect on tumor proliferation, it reduced myeloma BM egress and spreading to other bones, which improved overall survival as a single therapy and in combination with BM transplantation. Myeloma dissemination correlated with an increased inflammatory signature in BM MPs, as well as production of IL-6 and TNFα by tumor-associated MPs (TAMs). Exogenous i.v. IL-6 and TNFa could trigger myeloma intravasation in the BM by increasing vascular leakiness in the BM, and by enhancing myeloma motility by reducing CD138 adhesion. Moreover, mice lacking IL-6 had defects in myeloma dissemination as in MP-depleted recipients. While in TNFa or TNFaR deficient mice had defects in MM dissemination, engraftment was also impaired. These effects on myeloma dissemination required production of cytokines in the radiation-resistant compartment, containing these radiation-resistant BM MPs. Taken together, we propose BM egress of myeloma cells is regulated by localized inflammation in foci, driven in part by CD169 + MPs.
2021-06-09 | GSE176385 | GEO