Phase II study of single-agent daratumumab in patients with high-risk Monoclonal Gammopathy of Undetermined Significance (MGUS) and low-risk Smoldering Multiple Myeloma (SMM)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1288042 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Phase II study of single-agent daratumumab in patients with high-risk Monoclonal Gammopathy of Undetermined Significance (MGUS) and low-risk Smoldering Multiple Myeloma (SMM)
| PRJNA1288041 | ENA
Project description:MicroRNA expression profiles for human Multilple Myeloma and MGUS (monoclonal gammopathy of undetermined significance) were examined to investigate the miRNA involvement in the development of this neoplasia.
2008-09-03 | E-TABM-508 | biostudies-arrayexpress
Project description:Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genome-wide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, p=1.31×10-5) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, p=1.82×10-10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%) and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%) and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%) and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.
2016-02-18 | GSE77975 | GEO
Project description:Multiple myeloma is preceded by monoclonal gammopathy of undetermined significance (MGUS). Serum markers are currently used to stratify MGUS patients into clinical risk groups. A molecular signature predicting MGUS progression has not been produced. We have explored the use of gene expression profiling to risk-stratify MGUS and developed an optimized signature based on large samples with long-term follow-up. Microarray analysis of mRNA from MGUS patients with stable disease and MGUS patients that progressed to MM within 10 years, was used to define a molecular signature of MGUS risk.
2023-08-15 | GSE235356 | GEO
Project description:Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole-exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p<10-4) and we have identified six genes that are significantly mutated in MM (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with the primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however, overall genetic instability is significantly lower compared to MM.
2016-02-18 | GSE77979 | GEO
Project description:Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder, leading to the presence of monoclonal antibody (i.e., M-protein) in serum, without clinical symptoms. Here we present a case study in which we detect MGUS by liquid-chromatography coupled with mass spectrometry (LC-MS) profiling of IgG1 in human serum. We detected a Fab-glycosylated M-protein and determined the full heavy and light chain sequences by bottom-up proteomics techniques using multiple proteases, further validated by top-down LC-MS. Moreover, the composition and location of the Fab-glycan could be determined in CDR1 of the heavy chain.
2023-09-14 | PXD042266 | Pride
Project description:IgM monoclonal gammopathy of undetermined significance (IgM MGUS) is an early precursor stage of the rare lymphoma Waldenström Macroglobulinemia (WM). Although comparative gene expression studies on WM, IgM MGUS, and normal B cells identified several genes differently expressed, reliable predictors of progression from IgM MGUS to WM have not yet been identified. We performed a microarray study on CD19+ and CD138+ cells of WM vs. IgM MGUS vs. CTRLs to determine gene signatures for both cell populations. We demonstrated that hematopoietic antigens, cell-adhesion molecules, Wnt signaling, BCR signaling, calcium signaling, coagulation cascade, and pathways responsible for cell cycle and proliferation were significantly enriched for genes expressed in B cells of WM vs. IgM MGUS vs. CTRLs. Notably, we showed nine genes which displayed the same expression levels in both WM and IgM MGUS compared to CTRLs, suggesting their possible role in the risk of transformation in IgM MGUS to WM.
2021-04-09 | GSE171739 | GEO
Project description:To determine the cell types and their transcriptional alterations during multiple myeloma progression from its precursor conditions, ie. monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM), we used single-cell RNA sequencing (scRNA-seq) to analyze the bone marrow aspirate samples from 4 newly diagnosed multiple myeloma, 6 MGUS and 4 SMM patients as well as 5 healthy donors.
2024-07-04 | GSE271107 | GEO
Project description:Fibroblasts are a key cellular component of tumour microenvironment, along with other stromal cells playing a critical role in disease initiation and progression (1). In this study, bone marrow fibroblasts deriving from patients with monoclonal gammopathy of undetermined significance (MGUS) or active multiple myeloma (MM) were subjected to global gene expression analysis, in order to identify progression-associated alterations of gene expression. Through immunoselection procedures, primary cultures of bone marrow fibroblasts were established from bone marrow aspirate of 18 patients fullfilling the International Myeloma Working Group diagnostic criteria for MM (n=10) and MGUS (n=8). Differentially expressed genes were investigated through cDNA microarray (21,329 70-mer oligonucleotides; dual-label competitive hybridization), using the reference design as experimental protocol and t-test statistics for identifying differentially expressed genes. A number of genes functionally involved in survival, proliferation, motility, inflammation and angiogenesis were found to be up-regulated in bone marrow fibroblasts from MM patients with respect to MGUS patients. In parallel, several genes were down-regulated in MM fibroblasts. Overall, bone marrow fibroblasts from MM patients show a distinct gene expression pattern that differentiates them from bone marrow fibroblasts of MGUS. The observation of differentially expressed genes indicates an activation state of fibroblasts in MM, which very likely concur to determine a microenvironment supporting disease progression. 1. Kalluri R, Zeisberg M: Fibroblasts in cancer. Nat Rev Cancer 2006; 6: 392:401.
2010-10-30 | GSE24990 | GEO
Project description:Fibroblasts are a key cellular component of tumour microenvironment, along with other stromal cells playing a critical role in disease initiation and progression (1). In this study, bone marrow fibroblasts deriving from patients with monoclonal gammopathy of undetermined significance (MGUS) or active multiple myeloma (MM) were subjected to global gene expression analysis, in order to identify progression-associated alterations of gene expression. Through immunoselection procedures, primary coltures of bone marrow fibroblasts were established from bone marrow aspirate of 18 patients fullfilling the International Myeloma Working Group diagnostic criteria for MM (n=10) and MGUS (n=8). Differentially expressed genes were investigated through cDNA microarray (21,329 70-mer oligonucleotides; dual-label competitive hybridization), using the reference design as experimental protocol and t-test statistics for identifying differentially expressed genes. A number of genes functionally involved in survival, proliferation, motility, inflammation and angiogenesis were found to be up-regulated in bone marrow fibroblasts from MM patients with respect to MGUS patients. In parallel, several genes were down-regulated in MM fibroblasts. Overall, bone marrow fibroblasts from MM patients show a distinct gene expression pattern that differentiates them from bone marrow fibroblasts of MGUS. The observation of differentially expressed genes indicates an activation state of fibroblasts in MM, which very likely concur to determine a microenvironment supporting disease progression. 1) 1. Kalluri R, Zeisberg M: Fibroblasts in cancer. Nat Rev Cancer 2006; 6: 392 â401. Bone marrow fibroblasts deriving from patients with monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma (MM), were provided by A.Vacca, (Department of Biomedical Sciences and Human Oncology, Università degli Studi di Bari Aldo Moro, Italy). Briefly, primary coltures of bone marrow fibroblasts were established through immunoselection procedures on aspirates of 18 patients fullfilling the IMWG diagnostic criteria for active MM (n=10) and MGUS (n=8). Total RNA was extracted from each primary culture (test samples), and 1 μg-aliquots of RNA from MGUS samples were pooled to obtain the reference RNA. Linear amplification of mRNA and fluorescent labelling of cDNA targets (Cy5, MM and MGUS test samples; Cy3, reference RNA) were performed by using the Amino Allyl MessageAmp II aRNA Amplification Kit (Ambion), and examined on Micro-CRIBI Human Oligo Array (Operon V2.0) microarrays. Array scanning was carried out using a VersArray ChipReader® 5μm dual confocal laser scanner with VersArray ChipReader v3.1 analysis software , while row scanner images were analyzed with VersArray Analyzer Software v4.5 (Bio-Rad Laboratories) using media pixel intensities for each spot. Global background was subtracted by biquadratic polynomial approximation, and cross-channel normalization was performed by local regression (LOESS); logarithmic transformation was then performed for each expression level.
2010-10-30 | E-GEOD-24990 | biostudies-arrayexpress