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Transcriptomic analysis of VK12653 Multiple Myeloma bone marrow microenvironmentupon treatment with anti-CD137 agonists

ABSTRACT: Transcriptomic analysis of VK12653 Multiple Myeloma bone marrow microenvironmentupon treatment with anti-CD137 agonists

PROVIDER: PRJNA851353 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19762153_1.fastq.gz	Fastqsanger.gz
	SRR19762153_2.fastq.gz	Fastqsanger.gz
	SRR19762154_1.fastq.gz	Fastqsanger.gz
	SRR19762154_2.fastq.gz	Fastqsanger.gz
	SRR19762155_1.fastq.gz	Fastqsanger.gz

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Transcriptomic analysis of VK12653 Multiple Myeloma bone marrow microenvironmentupon treatment with anti-CD137 agonists

Project description:We report the RNA sequencing of VK12653 Multiple Myeloma bone marrow microenvironment upon treatment with anti-CD137 agonists

2023-06-30 | GSE206545 | GEO

Single cell Transcriptomic analysis of CD8+ T cells treated with anti-CD137 agonists within VK12653 Multiple Myeloma bone marrow microenvironment .

Project description:We report the single cell RNA sequencing of mouse CD8+ T cells infiltrating VK12653 Multiple Myeloma lesions upon treatment with anti-CD137 agonists .

2023-06-30 | GSE205702 | GEO

Single cell Transcriptomic analysis of CD8+ T cells treated with anti-CD137 agonists within VK12653 Multiple Myeloma bone marrow microenvironment .

Project description:Single cell Transcriptomic analysis of CD8+ T cells treated with anti-CD137 agonists within VK12653 Multiple Myeloma bone marrow microenvironment .

| PRJNA847213 | ENA

CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects

Project description:CD137 (4-1BB) is a member of the TNFR family that mediates potent T-cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies. CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models and multiple agents of this kind are undergoing clinical trials. We show that cIAP1 and cIAP2 are physically associated with the CD137-signaling complex. Moreover, cIAPs are required for CD137 signaling towards the NF-κB and MAPK pathways and for costimulation of human and mouse T lymphocytes. Functional evidence was substantiated with SMAC-mimetics that trigger cIAPs degradation and by transfecting cIAP dominant-negative variants. Antitumor effects of agonist anti-CD137 mAbs are critically dependent on the integrity of cIAPs in cancer mouse models and cIAPs are also required for signaling from CARs encompassing CD137’s cytoplasmic tail.

2024-05-24 | PXD042585 | Pride

Serum protein N-glycosylation changes in multiple myeloma

Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>

2022-04-27 | MTBLS676 | MetaboLights

Single cell Transcriptomic analysis of CD8+ T cells from bone marrow chimeras reconstituted with CD137 wild-type or knock out bone marrow, and implanted with B16K1 melanoma.

Project description:We report the single cell RNA sequencing of mouse CD8+ T cells in bone marrow chimeras reconsitituted with equal amounts of CD137-/-tomato+ and CD137-/-tomato- bone marrow implanted with B16K1 melanoma. CD8 T cells from the spleen or the tumor infiltrate are compared.

2023-06-30 | GSE205703 | GEO

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment

Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.

2018-10-24 | PXD006581 | Pride

microRNA profiling of multiple myeloma bone marrow

Project description:Bone marrow microenvironment in MM contains a unique miR signature, which is partially present and detectable in the peripheral blood. A subset of miRs (let-7i, miR-106b, miR-15a, and miR16) shows aberrant expression in the precursor lesion of MGUS, while aberrant expression of other miRs (let-7a, miR-15a/b, miR-19b, miR-20a, miR-21, miR-223, and miR-361) is associated with cell proliferation and disease progression. miRNA profiling was performed using Agilent miRNA array platforms with RNAs isolated from the bone marrow supernatant of multiple myeloma.

2016-07-01 | E-GEOD-49261 | biostudies-arrayexpress

Transcription profiling by array of human multiple myeloma cells and cell lines; bone marrow stromal cells, bone marrow CD3 cells, bone marrow CD14 cells, bone marrow CD15 cells and in vitro generated osteoclastic cells from myeloma patients; and normal plasmablasts and normal memory B cells.

Project description:Multiple Myeloma primary myeloma cells of 131 patients, 10 human myeloma cell lines, bone marrow stromal cells of 5 myeloma patients, bone marrow CD3 cells of 5 myeloma patients, bone marrow CD14 cells of 5 myeloma patients, bone marrow CD15 cells of 5 myeloma patients, in vitro generated osteoclastic cells of 7 myeloma patients, 7 normal plasmablasts and 6 normal memory B cells.

2011-03-08 | E-TABM-937 | biostudies-arrayexpress

Gene Expression Profiles of Multiple Myeloma

Project description:Samples in this series are pre-treatment bone marrow aspirates from multiple myeloma patients. Keywords = Multiple Myeloma, Bone Marrow, Pre-Treatment Keywords: other

2006-06-01 | GSE2658 | GEO

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