Gene expression signature predicting post-relapse survival of myeloma patients identified by co-culture of myeloma cells with osteoclasts and osteoblast progenitors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE31162 | GEO | 2015/08/13
SECONDARY ACCESSION(S): PRJNA144803
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-13 | E-GEOD-31162 | biostudies-arrayexpress
Project description:Gene expression signature predicting post-relapse survival of myeloma patients identified by co-culture of myeloma cells with osteoclasts and osteoblast progenitors
| PRJNA144803 | ENA
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of osteoclasts (OCs) before and after co-culture with primary multiple myeloma plasma cells (MMPCs) was done using Affymetrix microarrays. Eight MMPC and OC co-culture experiments were performed using MMPC isolated from 8 patients and OC prepared from 8 different patients.
2015-08-13 | E-GEOD-31156 | biostudies-arrayexpress
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of osteoclasts (OCs) before and after co-culture with primary multiple myeloma plasma cells (MMPCs) was done using Affymetrix microarrays.
2015-08-13 | GSE31156 | GEO
Project description:To understand how interactions of myeloma cells with osteoclasts and mesenchymal stem cells in the bone marrow affect the clinical course of myeloma, we used microarrays to study changes in gene expression in freshly isolated myeloma plasma cells following co-cultures with osteoclasts (8 experiments) or with mesenchymal stem cells (13 experiments). Interaction with osteoclasts induced changes in the expression of 675 genes, and interaction with mesenchymal stem cells induced changes in the expression of 296 genes. Expression of only 58 genes commonly and similarly changed in both co-culture systems. Among these, we identified genes associated with overall, progression-free, and post-relapse survival, and developed survival prediction models. Gene expression data from 347 patients treated with total therapy 2 protocol, 433 with total therapy 3, and 98 patients who received various treatments (91 of them high-dose therapy with autologous stem cell support) were used for the analysis. Good predictive models were developed only for post-relapse survival, using genes involved in interaction with osteoclasts or with mesenchymal stem cells. The best predictive model used expression of first relapse of 33 probesets whose expression changed in myeloma cells following interaction with osteoclasts, with hazard ratios of 24, 20, and 12 for patients who relapsed following total therapy 2, total therapy 3 and the various other treatments, respectively. Among the probesets used for prediction, only 10, representing 8 genes, were commonly changed after both co-culture systems. These could present favorable target for therapy. Global gene expression profiling of primary multiple myeloma plasma cells (MMPCs) before and after interaction with osteoclasts (OCs) was done using Affymetrix microarrays.
2019-08-21 | GSE31154 | GEO
Project description:The processes of bone resorption and bone formation are tightly coupled in young adults, which is crucial to maintenance of bone integrity. We have documented that osteoclasts secrete chemotactic agents to recruit osteoblast lineage cells, contributing to coupling. Bone formation subsequent to bone resorption becomes uncoupled with aging, resulting in significant bone loss. During bone resorption, osteoclasts release and activate transforming growth factor beta 1 (TGF-?1) from the bone matrix; thus, elevated bone resorption increases the level of active TGF-? in the local environment during aging. In this study, we examined the influences of TGF-?1 on the ability of osteoclasts to recruit osteoblasts. TGF-?1 increased osteoclast expression of the chemokine CXCL16 to promote osteoblast migration. TGF-?1 also directly stimulated osteoblast migration; however, this direct response was blocked by conditioned medium from TGF-?1-treated osteoclasts due to the presence of leukemia inhibitory factor (LIF) in the medium. CXCL16 and LIF expression was dependent on TGF-?1 activation of Smad2 and Smad3. These results establish that TGF-?1 induces CXCL16 and LIF production in osteoclasts, which modulate recruitment of osteoblasts to restore the bone lost during the resorptive phase of bone turnover.
| S-EPMC3845829 | biostudies-literature
Project description:Sox11 deletion mice are known to exhibit developmental defects of craniofacial skeletal malformations, asplenia, and hypoplasia of the lung, stomach, and pancreas. Despite the importance of Sox11 in the developing skeleton, the role of Sox11 in osteogenesis has not been studied yet. In this study, we identified that Sox11 is an important transcription factor for regulating the proliferation and survival of osteoblast precursor cells as well as the self-renewal potency of mesenchymal progenitor cells via up-regulation of Tead2. Furthermore, Sox11 also plays an important role in the segregation of functional osteoblast lineage progenitors from osteochondrogenic progenitors. Facilitation of osteoblast differentiation from mesenchymal cells was achieved by enhanced expression of the osteoblast lineage specific transcription factors Runx2 and Osterix. Morpholino-targeted disruption of Sox11 in zebrafish impaired organogenesis, including the bones, which were under mineralized. These results indicated that Sox11 plays a crucial role in the proliferation and survival of mesenchymal and osteoblast precursors by Tead2, and osteogenic differentiation by regulating Runx2 and Osterix.
| S-EPMC3757203 | biostudies-literature
Project description:Bone tissue undergoes constant remodeling and healing when fracture happens, in order to ensure its structural integrity. In order to better understand open biological and clinical questions linked to various bone diseases, bone cell co-culture technology is believed to shed some light into the dark. Osteoblasts/osteocytes and osteoclasts dominate the metabolism of bone by a multitude of connections. Therefore, it is widely accepted that a constant improvement of co-culture models with both cell types cultured on a 3D scaffold, is aimed to mimic an in vivo environment as closely as possible. Although in recent years a considerable knowledge of bone co-culture models has been accumulated, there are still many open questions. We here try to summarize the actual knowledge and address open questions.
| S-EPMC6121694 | biostudies-literature
Project description:Osteoclasts are highly specialized cells of haematopoietic lineage that are uniquely responsible for bone resorption. In the past, osteoclasts were isolated as mature cells from chicken long bones, or were generated using osteoblasts or stromal cells to induce osteoclast formation in total bone marrow from mice or rabbits. The Copernican revolution in osteoclast biology began with the identification of macrophage-colony stimulating factor (M-CSF) and receptor activator NFκB-ligand (RANKL ) as the key regulators of osteoclast formation, fusion and function. The availability of recombinant human and mouse M-CSF and RANKL has enabled researchers to reliably generate osteoclasts from primary monocyte/macrophage cells as well as from cell lines such as RAW 264.7. This article summarizes the most commonly used procedures for the isolation, generation and characterization of human, rodent and chicken osteoclasts in vitro. Lists of further reading and recommendations are included to facilitate a successful application by the reader.
| S-EPMC4162467 | biostudies-other
Project description:The goal of this study was to explore quantitative assessments of mineralized silk protein biomaterial films by co-cultures of human mesenchymal stem cell-derived osteoblasts and human acute monocytic leukemia cell line-derived osteoclasts during long-term culture (8-32 weeks). The remodeled films were quantitatively assessed using three different techniques during this extended cultivation to provide more comprehensive insight into the impact of co-cultures on surface remodeling. Scanning electron microscopy (SEM) with three dimensional surface reconstructions was used to quantitatively determine various surface morphological features and measures of roughness indicative of remodeling by the cells. Additionally, reconstructed surfaces were converted to depth images for Fourier analysis to quantify the potential fractal organization of biomineralization. The long-term remodeled films were also imaged using confocal reflectance microscopy and micro-computed tomography (micro-CT) to further quantify morphological changes. Films remodeled in co-culture demonstrated increased roughness parameters, fractal organization, and volume compared to films remodeled by osteoblasts alone. The combination of these techniques to quantify remodeling of mineralized protein films shows promise for quantifying processes related to mineralized surfaces.
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