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Gene expression profiling of mesenchymal stem cells from bone marrow of multiple myeloma patients and normal donors

ABSTRACT: A growing body of evidence points to the essential role of bone marrow (BM) tumor microenvironment in Multiple Myeloma (MM) maintenance and progression. Mesenchymal stem cells (MSC) are one of the most important players in this scenario. Through direct and indirect interactions, these cells support MM cells by promoting increase of proliferation, migration, survival, and drug resistance. Additionally, an increasing number of evidence has been demonstrating that MSC from MM patients (MM-MSC) have several abnormalities when compared with their normal counterpart from normal donors (ND-MSC). Therefore, the aimed of our study was to explore the differences between MM-MSC and ND-MSC through gene expression analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113736 | GEO | 2019/01/21

REPOSITORIES: GEO

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Expression data from bone marrow mesenchymal stromal cells obtained from healthy donors and myeloma patients

Project description:Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone marrow (BM) compartment, where they acquire resistance to chemotherapy-mediated apoptosis. Natural history of patients include a premalignant stage, the MM diagnosis, the treatment, the remission, and for most of them the relapse. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients are functionally different from healthy donors (HD) MSC and display a distinct transcriptome. They have been largely involved in MM pathogenesis and chemoresistance acquisition. In order to determine if MM-MSC also participate to relapse, we focused on the characterization of MSC from patients with MM at different stages of the disease. We obtained patient MSC’s samples at diagnosis, at 2 years after intensive treatment without relapse and at the relapse from an intensive treatment. We used MCS from HD as control. All MSC were able to support MM cells growth through released factors, and still multipotent since able to differentiate into osteoblast and adipocyte. A transcriptomic analysis between these groups reveals differences in gene expression between HD and MM MSC whatever stage of the disease, suggesting that the difference in gene expression in MM-MSC persist with time. These data demonstrate an imprinting of MSC as soon as they were in contact with MM cells, which persist even after the disappearance of MM cells. This imprinting is in favour of an easier differentiation towards adipogenesis.

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bulk RNA-seq data analysis of primary human mesenchymal stem cells of Multiple Myeloma patients compared to control patients

Project description:Purpose: In this study we compared bone marrow-derived mesenchymal stem cells (MSC) of 6 Multiple Myeloma patients (MM-MSC) with MSC of 5 control donors with other (non) malignant diseases (CTR-MSC) to detect transciptomic alterations in RNA sequencing and to identify altered gene expression patterns. Methods: MSC were obtained from bone marrow, cultivated, analyzed by flow cytometry and underwent quality control using the 4200 TapeStation (Agilent, California, USA). Following the TrueSeq stranded protocol (Illumina, California, USA) we sequenced the RNA in a 100 bp paired-end run on the HiSeq 4000 (Illumina). Results: We detected 2174 significant DEGs (adjusted p<0.05) between MM-MSC and CTR-MSC, among which 967 were up-regulated in MM-MSC. 18 out of 50 MSigDB Hallmark gene sets were significantly enriched in MM-Act-MSC compared to CTR-MSC (FDR<0.05) including PI3K-AKT-mTOR signaling, as well as NOTCH, MYC and Inflammatory response. Conclusion: Our data provides a deeper insight into the molecular signature and function of MSC associated MM-cells and show that targeting PI3K-AKT-mTOR signaling in MSC may represent an additional therapeutic pathway in the treatment of MM-patients.

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Comparison of bone-marrow mesenchymal stromal cells from multiple myeloma patients and healthy donors

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Expression data from exosomes

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