Mucin 1 knockdown in EMM myeloma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE114885 | GEO | 2019/01/31
REPOSITORIES: GEO
Similar Datasets
Project description:Mucin 1 knockdown in EMM myeloma cells
| PRJNA472976 | ENA
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
Project description:Forkhead Box M1 (FOXM1) is a promising molecular target for high-risk multiple myeloma and relapse and refractory myeloma, but whether FOXM1 is essential in myeloma has not yet been established. To address this knowledge gap, we used Western blotting to measure FOXM1 protein levels in 11 human myeloma cell lines (HMCLs) and then chose the two lines expressing the largest amount of the transcription factor, OPM2 and Delta47, for gene editing using CRISPR-Cas9. In both cases, two independent FOXM1-deficient daughter lines, designated KO-1 and KO-2, were generated. They contained 2 different 10-bp deletions at the target site of their respective guide RNA in case of OPM2 and a 10-bp deletion and 1-bp insertion in case of Delta47. Western analysis confirmed the lack of FOXM1 in all knockout clones. FOXM1-deficient myeloma cells proliferated more slowly than their parental counterparts containing normal levels of FOXM1. Moreover, we added back FOXM1 to FOXM1-KO cells by transfection of a constitutively expressed FOXM1c cDNA gene. The reconstituted OPM2 and Delta47 cells, designated FOXM1 KO-R contained high amounts of FOXM1 protein. Here, we used these cell lines to investigate the role of FOXM1 in regulating the gene expression in multiple myeloma.
2021-07-14 | GSE180018 | GEO
Project description:8 pairs of myeloma cell lines were sorted by MACS CD138-microbead, and the each cell lines were divided into two fraction CD138+ and CD138-. We used microarrays to detail the global programme of gene expression in these 8 pairs of CD138+/- myeloma cell lines CD138- fraction in myeloma are thought to be myeloma stem cells fraction, and we compared the gene expression profile between CD138- and CD138+ fraction.
2013-09-05 | E-GEOD-46816 | biostudies-arrayexpress
Project description:Bifidobacteria constitute commensal bacteria that commonly inhabit the mammalian gastro intestinal tract. The gut commensal Bifidobacterium breve UCC2003 was previously shown to utilise a variety of plant/diet-derived carbohydrates, including cellodextrin, starch and galactan. In the current study, we investigated the ability of this strain to utilize (parts of) a host-derived source of carbohydrate, namely the mucin glycoprotein. Here, we demonstrate that B. breve UCC2003 exhibits growth properties in a mucin-based medium, but only when in the presence of Bifidobacterium bifidum PRL2010, which is known to metabolize mucin. Based on HPAEC analysis, transcriptome data and insertion mutagenesis, it appears that B. breve UCC2003 sustains this improved survival in co-culture by cross-feeding on a combination of fucose, sialic acid and galactose-containing oligosaccharides.
2014-12-17 | GSE59013 | GEO
Project description:8 pairs of myeloma cell lines were sorted by MACS CD138-microbead, and the each cell lines were divided into two fraction CD138+ and CD138-. We used microarrays to detail the global programme of gene expression in these 8 pairs of CD138+/- myeloma cell lines
2013-09-05 | GSE46816 | GEO
Project description:The myeloma cell surface proteome (“surfaceome”) not only determines tumor interaction with the microenvironment but serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to first define surface markers most-enriched on myeloma when compared to B-cell malignancy models, revealing unexpected biological signatures unique to malignant plasma cells. We next integrate our proteomic dataset with existing transcriptome databases, nominating CCR10 and TXNDC11 as possible monotherapeutic targets and CD48 as a promising co-target for increasing avidity of BCMA-directed cellular therapies. We further identify potential biomarkers of resistance to proteasome inhibitors and lenalidomide including changes in CD53, EVI2B, CD10, and CD33. Comparison of short-term treatment with chronic resistance delineates large differences in surface proteome profile under each type of drug exposure. Finally, we develop a miniaturized version of the surface proteomics protocol and present the first surface proteomic profile of a primary MM patient plasma cell sample. Our dataset provides a unique resource to advance the biological, therapeutic, and diagnostic understanding of myeloma.
2022-05-27 | PXD022553 | Pride
Project description:The myeloma cell surface proteome (“surfaceome�) not only determines tumor interaction with the microenvironment but serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to first define surface markers most-enriched on myeloma when compared to B-cell malignancy models, revealing unexpected biological signatures unique to malignant plasma cells. We next integrate our proteomic dataset with existing transcriptome databases, nominating CCR10 and TXNDC11 as possible monotherapeutic targets and CD48 as a promising co-target for increasing avidity of BCMA-directed cellular therapies. We further identify potential biomarkers of resistance to proteasome inhibitors and lenalidomide including changes in CD53, EVI2B, CD10, and CD33. Comparison of short-term treatment with chronic resistance delineates large differences in surface proteome profile under each type of drug exposure. Finally, we develop a miniaturized version of the surface proteomics protocol and present the first surface proteomic profile of a primary MM patient plasma cell sample. Our dataset provides a unique resource to advance the biological, therapeutic, and diagnostic understanding of myeloma. Note that this is a data supplement to PXD022553.
2022-05-27 | PXD032031 | Pride
Project description:Multiple myeloma (MM) progression is linked to chronic NF-κB activation in myeloma cells. However, the identity and source of autocrine/paracrine signals driving NF-κB activation and the role of the 3D microenvironment have been scarcely investigated both in vivo and in vitro. To investigate them, we knocked-in the Venus (YFP) ORF in the NF-κB p65 gene in both MM and stromal cells. Surprisingly, a large fraction of p65-YFP MM cells engrafted in mouse bone marrow showed overall low levels of NF-κB activation whereas a small fraction was highly activated. To understand these in vivo data, we investigated NF-κB dynamics in MM and stromal cells, both alone and in co-culture. In vitro experiments exploiting microfluidics, bioreactor and microchip cell cultures highlighted crosstalk between the myeloma and stromal components that leads to mild basal activation. In contrast, we found that high-density cultures within 3D scaffolds dampen NF-κB activation in MM and stromal cells, both in basal and inflammatory conditions. It has been recently hypothesized that IL1β, and the inflammatory ME, shape the overall activity of ME components and promote the transition of Mesenchimal Stromal Cells (MSCs) toward an inflammatory NF-κB driven transcriptional phenotype (iMSCs). We tested this hypothesis in our system and found that IL1β strongly activates NF-κB in stromal but not in myeloma cells. In addition, secreted molecules from IL1β-stimulated MSCs strongly activate NF-κB only in a small fraction of MM cells. We propose that the balance between activating stimuli from iMSCs and dampening feedbacks from the 3D ME, maintains a mild NF-κB activation in myeloma cells in the patients’ BM to avoid exceedingly harmful responses.
2024-11-05 | GSE197936 | GEO
Project description:A major driver of multiple myeloma is thought to be aberrant signaling, yet no kinase inhibitors have proven successful in the clinic. Here, we employ an integrated, systems approach combining phosphoproteomic and transcriptome analysis to dissect cellular signaling in multiple myeloma to inform precision medicine strategies. Collectively, these predictive models identify vulnerable signaling signatures and highlight surprising differences in functional signaling patterns between <I>NRAS</I> and <I>KRAS</I> mutants invisible to the genomic landscape. Transcriptional analysis suggests that aberrant MAPK pathway activation is only present in a fraction of <I>RAS</I>-mutated vs. WT <I>RAS</I> patients. These high-MAPK patients, enriched for <I>NRAS</I> Q61 mutations, have inferior outcomes whereas <I>RAS</I> mutations overall carry no survival impact. We further develop an interactive software tool to relate pharmacologic and genetic kinase dependencies in myeloma. These results may lead to improved stratification of MM patients in clinical trials while also revealing unexplored modes of Ras biology.
2019-03-06 | PXD011551 | Pride