Affymetrix SNP array data for Monoclonal Gammopathies samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Maria Sarasquete
PROVIDER: E-GEOD-31339 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Although information on the molecular pathogenesis of Waldenström’s Macroglobulinemia (WM) has greatly improved in recent years, the exact cellular origin and the mechanisms behind WM transformation from IgM MGUS remain undetermined. Here, we undertook an integrative phenotypic, molecular and genomic approach to study clonal B-cells from newly-diagnosed patients with IgM MGUS (n=22), smoldering (n=17), and symptomatic WM (n=10). Through principal-component-analysis of multidimensional flow cytometry data, we demonstrated overlapping phenotypic profiles between clonal B-cells from IgM MGUS, smoldering and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between FACS-sorted clonal B-cells from the three disease stages. Interestingly, while the transcriptome of the Waldenström’s clone was highly deregulated as compared to CD25-CD22+ normal B-cells, significantly less genes were differentially expressed and specific WM pathways down-regulated while comparing the transcriptome of the Waldenström’s clone vs. its normal phenotypic counterpart: CD25+CD22+dim B-cells. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs. symptomatic WM (18% vs. 20% and 73%, respectively; P =.008), suggesting a multistep transformation of clonal B-cells that albeit benign (i.e.: IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström’s clone. Copy number analysis using the Affymetrix CytoScan 750K Array to study clonal B-cells from newly-diagnosed patients with IgM MGUS, smoldering, and symptomatic WM. Peripheral T-cells from paired and unpaired controls were also assessed.
2015-05-06 | E-GEOD-61650 | biostudies-arrayexpress
Project description:To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell (NPC) to a clonal PC and from an indolent clonal PC to a malignant PC, we performed gene expression profiling in 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. The analysis showed that 126 genes were differentially expressed in MGUS, SMM and MM as compared to NPC. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules (snoRNA) and zinc finger proteins. GADD45A was the most significant up-regulated gene in clonal PC compared to NPC. Several proapoptotic genes (AKT1 and AKT2) were downregulated and antiapoptotic genes (APAF1 and BCL2L1) were upregulated in MM, both symptomatic and asymptomatic, compared to MGUS. Myc mediated apoptosis signaling is one of the top canonical pathways differentiating the asymptomatic and symptomatic myeloma. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation in the transition from MGUS to SMM and to MM. In conclusion, our data show that although MGUS, SMM and MM are not clearly distinguishable groups according to their GEP, several signaling pathways and genes were significant deregulated in the different steps of transformation process.
2014-05-22 | GSE47552 | GEO
Project description:To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell (NPC) to a clonal PC and from an indolent clonal PC to a malignant PC, we performed gene expression profiling in 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. The analysis showed that 126 genes were differentially expressed in MGUS, SMM and MM as compared to NPC. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules (snoRNA) and zinc finger proteins. GADD45A was the most significant up-regulated gene in clonal PC compared to NPC. Several proapoptotic genes (AKT1 and AKT2) were downregulated and antiapoptotic genes (APAF1 and BCL2L1) were upregulated in MM, both symptomatic and asymptomatic, compared to MGUS. Myc mediated apoptosis signaling is one of the top canonical pathways differentiating the asymptomatic and symptomatic myeloma. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation in the transition from MGUS to SMM and to MM. In conclusion, our data show that although MGUS, SMM and MM are not clearly distinguishable groups according to their GEP, several signaling pathways and genes were significant deregulated in the different steps of transformation process. Bone marrow (BM) samples were obtained from 20 patients with MGUS, 33 with high-risk SMM and 41 with MM. All samples corresponded to newly diagnosed untreated patients. To avoid misclassification or overlapping entities we decided to focus on MGUS patients with more than two years of stable follow-up. Samples were classified according to the International Myeloma Working Group criteria. The criteria for defining high-risk SMM has been described previously. In addition, five healthy donors were also included in order to relate the deregulation of gene expression profiling of clonal populations to normal condition. The study was approved by the research ethic committees of all participating centers and written informed consent was obtained from all patients in accordance with the Helsinki Declaration. The main clinical and laboratory characteristics of these patients are shown in Supplementary Table 1.
2014-05-22 | E-GEOD-47552 | biostudies-arrayexpress
Project description:Gene expression profiling of bone marrow-derived mesenchymal stromal cells from healthy donors (n=8), monoclonal gammopathy of undetermined significance (MGUS) (n=10), smoldering myeloma (SMM) (n=10) and multiple myeloma (MM) (n=24) patients. Gene expression profile of MSCs was obtained using high density oligonucleotide microarrays (Human Gene 1.0 ST Array from Affymetrix).
2020-11-25 | GSE137369 | GEO
Project description:Genome wide DNA methylation profiling of bone marrow-derived mesenchymal stromal cells from healthy donors (n=11), monoclonal gammopathy of undetermined significance (MGUS) (n=10), smoldering myeloma (SMM) (n=8), multiple myeloma (MM) (n=9) patients, and healthy donors exposed to the MM.1S cell line (n=3). The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in this cell type.
2020-11-25 | GSE137416 | GEO
Project description:Genome wide DNA methylation profiling of bone marrow-derived mesenchymal stromal cells from healthy donors (n=11), monoclonal gammopathy of undetermined significance (MGUS) (n=10), smoldering myeloma (SMM) (n=8), multiple myeloma (MM) (n=9) patients, and healthy donors exposed to the MM.1S cell line (n=3). The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in this cell type.
2020-11-25 | GSE137360 | 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:Multiple Myeloma (MM) is an incurable plasma cell malignancy primarily localized within the bone marrow (BM). It develops from a premalignant stage, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage, smoldering MM (SMM). The mechanisms of MM progression have not yet been fully understood, all the more because patients with MGUS and SMM already carry the same initial mutations found in MM cells. Over the last years, more and more importance has been attributed to the tumor microenvironment and its role in the pathophysiology of the disease. Adaptations of MM cells to the hypoxic conditions in the BM have been shown to contribute to a significant extent to MM progression, independently from the genetic predispositions of the tumor cells. To get deeper insights into such hypoxia-induced adaptations, we decided to investigate primary human MM cells. CD138-positive plasma cells freshly isolated from the BM of patients with different disease stages, comprising MGUS, SMM, and MM, were analyzed by proteome profiling using a Q Exactive orbitrap. Data previously obtained from peripheral B cells were included for comparative purposes. As a first, rather unexpected result, we were able to identify three clusters differentiating B cells as well as MM cells corresponding to less and more advanced disease stages. Comparing on the one hand B cells to MM cells, and on the other hand the two clusters of MM cells allowed us to determine transcription factors apparently involved in MM development and progression, as well as protein regulatory networks obviously related to metabolic adaptations and immune evasion strategies used by MM cells to overcome limitations imposed by hypoxia. Based on these results, new opportunities may arise for developing therapeutic strategies targeting the progression from less to more advanced stages of MM.
2019-02-27 | PXD010600 | Pride
Project description:Smoldering myeloma (SMM) is a pre-malignant monoclonal gammopathy with a 10% annual risk to progress to active multiple myeloma (MM). SMM diagnostic criteria, as well of those of others monoclonal gammopathies, have been updated by the International Myeloma Working Group (IMWG) in 2014. In particular, the previously defined “ultra high-risk” SMM (characterized by the presence of specific biomarkers associated with a ≥ 80% risk of progression to symptomatic MM within 2 years) has been included among patients with active MM. SMM is biologically heterogeneous, including a subset of patients with biological pre-malignancy and a subset with biological malignancy who have not yet developed organ damage, defined as onset of the classical CRAB criteria or Myeloma Defining Events (MDE). Thus, SMM encompassed patients with a very low rate of progression to symptomatic MM, similar to patients with monoclonal gammopathy of uncertain significance (MGUS), as well as patients who acquired organ damage and progress to active MM within the first year from diagnosis. The molecular mechanisms involved in the SMM to MM progression are still far to be fully understood. Genomic studies indicate that the genetic alterations that characterize MM patients are already present in SMM ones, who present similar mutational and copy number alteration load. However, few data are available on the transcriptional profiles of SMM patients in relationship to the progression to active MM, overall indicating minimal differential expression either in coding or non-coding RNA fraction. To date, robust data are still lacking which describe the transcriptional profiles of plasma cells (PCs) from paired samples obtained at the time of SMM and at MM onset. Herein, we compared the transcriptome of purified CD138+ PCs from paired samples of SMM patients progressed to active MM (P-SMM), aimed at describing any possible common transcriptional discrepancy that may help to understand the intra-patient disease evolution; at the same time, we investigated the transcriptional differences between P-SMM and a subset of non-progressed SMM (NP-SMM) at a minimum of 36 months.
2019-07-17 | GSE117847 | GEO
Project description:Precursor states of Multiple Myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, MGUS and smoldering myeloma (SMM), to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient progression. We find NK cell abundance is frequently increased in early stages, and associated with altered chemokine receptor expression. As early as SMM, we show loss of GrK+ memory cytotoxic T-cells, and show their critical role in MM immunosurveillance in mouse models. Finally, we report MHC class II dysregulation in CD14+ monocytes, which results in T cell suppression in vitro. These results provide a comprehensive map of immune changes at play over the evolution of pre-malignant MM, which will help develop strategies for immune-based patient stratification.
2020-04-28 | GSE124310 | GEO