Microarray analysis to identify the molecular mechanisms whereby pDCs confer growth and drug resistance in MM cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE17407 | GEO | 2009/07/31
SECONDARY ACCESSION(S): PRJNA118859
REPOSITORIES: GEO
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Project description:Multiple Myeloma (MM) remains incurable despite novel therapies, suggesting the need for further identification of factors mediating tumorigenesis and drug resistance. We performed microarray analysis to identify the molecular mechanisms whereby pDCs confer growth and drug resistance in MM cells. Comparsion of MM cells in the presence and absence of pDCs (plasmacytoid dendritic cells)
2009-07-31 | E-GEOD-17407 | biostudies-arrayexpress
Project description:Analysis of gene expression change induced by myeloma cells in pDCs. The hypothesis tested in the present study was that myeloma cells inhibit pDCs function by direct contact. Results provide important information of gene expression change in the cocultured of pDCs and myeloma, such as IFNs and IFN regulatory genes, TLR9 signaling pathways.
2018-04-26 | GSE113647 | GEO
Project description:Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF-κB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and delayed the survival of MM tumour-bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKCδ, which played an important role in activating the canonical NF-κB signalling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF-κB signalling by the small-molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug-resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM.
2023-08-18 | GSE240978 | GEO
Project description:Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1-6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the global proteome in MM cells and the stromal cell line HS-5 to reveal hypoxia-dependent regulation of proteins.
2022-02-16 | PXD030239 | Pride
Project description:Microarray analysis to identify the molecular mechanisms whereby pDCs confer growth and drug resistance in MM cells
| PRJNA118859 | ENA
Project description:Multiple Myeloma (MM) is an incurable malignancy characterised by alterations of coding and non-coding genes that promote tumour growth and drug resistance. Despite the crucial role of long non-coding-RNAs (lncRNAs) in myeloma genesis is established, the functional role of the non-coding RNAome in MM remains largely unknown. We performed an unbiased CRISPR-Cas9 recessive screen targeting 671 lncRNAs in MM cell lines unvealing and prioritising a list of novel onco-lncRNAs essential for MM cell fitness and associated with high expression and poor prognosis in MM patients. Among them, RP11-350G8.5 emerged as the most promising vulnerability for MM cells, irrespective of their resistance to the standard-of-care bortezomib. We i) validated the oncogenic role of RP11-350G8.5 in vitro and in vivo; ii) characterised its function in relation to the unfolded protein stress response and induction of immunogenic cell death, and iii) shed light on its sub-cellular localisation, structural and chemical predictions of RNA-G-quadruplex-forming regions to pave the way to the development of novel therapeutics.
2024-08-20 | GSE273796 | GEO
Project description:Venetoclax is the first example of personalized medicine for multiple myeloma (MM), with meaningful clinical activity as a monotherapy and in combination in myeloma patients harboring the t(11:14) translocation. However, despite the high response rates and prolonged PFS, a significant proportion of patients eventually relapse. Here, we aimed to study adaptive molecular responses after the acquisition of venetoclax resistance in sensitive t(11:14) MM cell models. We therefore generated single-cell venetoclax-resistant t(11:14) MM cell lines and investigated the mechanisms contributing to resistance as well as the cells’ sensitivity to other treatments. Our data suggests that acquired resistance to venetoclax is characterized by reduced mitochondrial priming and changes in BCL-2 family proteins’ expression in MM cells, conferring broad resistance to standard-of-care anti-myeloma drugs. However, our results show that the resistant cells are still sensitive to immunotherapeutic treatments, highlighting the need to consider appropriate sequencing of these treatments following venetoclax-based regimens.
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Project description:Multiple Myeloma (MM) is cancer in the antibody-producing plasma cells. It comprises 1 percent of all hematological malignancies. MM is incurable and fatal. The proteasome inhibitor bortezomib has improved treatment significantly, but inherent and acquired resistance remains a problem. Glutathione (GSH) is an important red-ox buffer in eukaryotic cells. In this experiment we investigate how GSH affects bortezomib-induced gene expression changes
2014-08-01 | E-MTAB-2666 | biostudies-arrayexpress
Project description:Insights into mechanisms involved during intra-medullary myeloma progression could be helpful in the better understanding of this disease and in the development of new therapeutical strategies. Herein gene expression profile of multiple myeloma (MM) cells during intra-medullary progression was investigated using the 5T2MM murine model. MM-cells from 3 subsequent disease stages, quiescent, intermediate and end stage were analyzed using microarrays containing 21,492 Unigene cDNA sequences. ~ 3000 calls of differentially expressed genes were obtained. Most of these genes were silenced during tumor progression. In the early stage the MM-cells had up-regulated genes involved in bone marrow (BM) homing (CCR2, CCR5), motility (tetraspanins, 67kD laminin receptor, paxillin, zyxin, prolactin receptor), invasion (annexin II, cathepsins), adhesion (integrins, ALCAM) and cell adhesion mediated drug resistance (fibronectin). Genes involved in apoptosis (Mcl-1), plasma cell differentiation (XBP-1), angiogenesis (neuropilin-2, angiopoietin-like 4), hypoxia (HIF-1a, carbonic anhydrase 9) and in retention (CXCR4/CXCL12) and anchoring of MM-cells (laminin, collgens) in the BM were up-regulated during progressive stages. Quantative RT-PCR confirmed the trend of expression. These data provide a framework of mechanisms involved in intra-medullary myeloma progression; several genes known to be important in MM-biology are highlighted and novel candidate genes are illuminated as potentially more effective therapeutical targets.
2008-03-27 | E-MEXP-186 | biostudies-arrayexpress
Project description:Bone marrow -adipocytes (BMAs) have recently been implicated in accelerating bone metastatic cancers such as AML and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity- two key risk factors in multiple myeloma (MM) disease prevalence- suggesting that BMAs influence and are influenced by myeloma cells in the marrow. Here we examined how myeloma cells affect adipocytes and provide evidence that MM cells alter adipocyte gene expression and cytokine secretion profiles, creating a “MM-associated” adipocyte (MM-adipocyte) phenotype. Our findings indicate that: (1) Multiple myeloma cells decrease BM adiposity in vitro, in myeloma animal models, and in clinical samples, (2) myeloma induces widespread gene expression and phenotypic changes in adipocytes in vitro, most notable, the induction of a senescent-like phenotype in BMAs, (3) MM-adipocytes affect myeloma cell cycle, drug sensitivity, and aggressiveness, illuminating a new driver of MM cell evolution in a drug resistant clone. We demonstrate that myeloma cells exposed to MM-adipocytes are rescued from dexamethasone-induced cell cycle arrest and have increased expression of FKBP5, a potential drug resistance gene. Our findings in patients confirm that BMAs are dynamic during myeloma disease progression (decrease during MM initiation, recover during disease remission) and that the interactions between BMAs and MM cells have previously unappreciated implications in the understanding and treatment of myeloma.
2021-03-10 | GSE140374 | GEO