Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell RNA sequencing of multiple myeloma I

ABSTRACT: To understand molecular events associated with myeloma progression, we applied single-cell RNA sequencing to myeloma cells in the bone marrow and extramedullary sites. Transcriptome analysis, at single cell level, demonstrates that proliferation and alterations in antigen presentation are associated with myeloma progression whereas NF-kB pathway activation has an anti-correlation. While these alterations are prominent in most of the extramedullary myeloma cells, some myeloma cells in the bone marrow show gene expression signatures resembling extramedullary cells even when the myeloma cells were taken at stable disease. Altogether single-cell transcriptome analysis reveals both common transcriptional programs and heterogeneity turned on during myeloma progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106218 | GEO | 2019/10/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Clonal cytogenetics changes in progression of multiple myeloma to extramedullary relapse and plasmocellular leukemia – case report

2015-10-10 | E-MTAB-3577 | biostudies-arrayexpress

Single cell RNA sequencing revealed a chemokine self-feeding of myeloma cells for extramedullary metastasis

Project description:To determine the mechanisms of the initial extramedullary translocation of myeloma cells from bone marrow into peripheral blood. We found that the clonal cPCs were more frequently detected by flowcytometry in extramedullary plasmacytoma patients and worsened their prognosis. It is technically much easier to collect single cPCs using FACS than it is to perform EMP biopsy. Combining imaging extramedullary plasmacytoma diagnosis and cPCs detection may be a promising strategy for prognostic stratification. Using single-cell transcriptome analysis, we found that CXCL12, a key molecule for the CXCR4-dependent cell retention mechanism in bone marrow, was abnormally up-regulated in cPCs and might initially enable cPCs evasion and translocation into blood.

2019-09-18 | GSE137545 | GEO

Intratumor Heterogeneity of MIF Expression Correlates with Extramedullary Involvement of Multiple Myeloma

Project description:Macrophage migration inhibitory factor (MIF) has been shown to promote disease progression in many malignancies, including multiple myeloma (MM). We previously reported that MIF regulates MM bone marrow homing and knockdown of MIF favors the extramedullary myeloma formation in mice. Here, based on MIF immunostaining of myeloma cells in paired intramedullary and extramedullary biopsies from 17 patients, we found lower MIF intensity in extramedullary MM (EMM) versus intramedullary MM (IMM). Flow cytometry and histology analysis in ARD cell line-derived xenograft models showed a portion of inoculated human MM cells lost their MIF expression (MIFLow) in vivo. Of note, IMM had dominantly MIFHigh cells, while EMM showed a significantly increased ratio of MIFLow cells. We harvested the extramedullary human MM cells from a mouse and generated single-cell transcriptomic data. The developmental trajectories of MM cells from the MIFHigh to MIFLow state were indicated. The MIFHigh cells featured higher proliferation. The MIFLow ones were more quiescent and harbored abundant ribosomal protein genes. Our findings identified in vivo differential regulation of MIF expression in MM and suggested a potential pathogenic role of MIF in the extramedullary spread of disease.

2021-07-20 | GSE175660 | GEO

Bone Marrow Stromal Cells Induce Chromatin Remodeling in Multiple Myeloma Cells Leading to Transcriptional Changes [Multiome (10X Genomics) - scRNA-Seq & scATAC-Seq]

Project description:The natural history of multiple myeloma is characterized by its localization to the bone marrow and its interaction with bone marrow stromal cells. The bone marrow stromal cells provide growth and survival signals, thereby promoting the development of drug resistance. Here, we show that the interaction between bone marrow stromal cells and myeloma cells (using human cell lines) induces chromatin remodeling of cis-regulatory elements and is associated with changes in the expression of genes involved in the cell migration and cytokine signaling. The expression of genes involved in these stromal interactions are observed in extramedullary disease in patients with myeloma and provides the rationale for survival of myeloma cells outside of the bone marrow microenvironment. Expression of these stromal interaction genes is also observed in a subset of patients with newly diagnosed myeloma and are akin to the transcriptional program of extramedullary disease. The presence of such adverse stromal interactions in newly diagnosed myeloma is associated with accelerated disease dissemination, predicts the early development of therapeutic resistance, and is of independent prognostic significance. These stromal cell induced transcriptomic and epigenomic changes both predict long-term outcomes and identify therapeutic targets in the tumor microenvironment for the development of novel therapeutic approaches.

2024-04-04 | GSE263178 | GEO

Clonal cytogenetics changes in progression of multiple myeloma to extramedullary relapse and plasmocellular leukemia – case report

Project description:Extramedullary relapse (EM) of multiple myeloma (MM) is defined as infiltration of plasma cells (PC) outside of the bone marrow. EM is an aggressive form of the disease with a dismal outcome. We present cytogenetic findings of a 52-year-old female patient who was diagnosed with MM in 2008 and progression of MM to EM and plasmocellular leukemia retrospective analysis of TP53 mutation status showed presence of 2 known missense mutations in exon 6 (c.632C>T) and exon 7 (c.700T>C). EM relapse of this patient was connected to a change of the entire genome profile. We suppose that the extramedullary lesion originated by an expansion of one clone of tumor plasma cells from the bone marrow, which was confirmed by identical genomic profile of both tested samples. Thus, change of ploidy status should be considered as potential hallmark of adverse course of the disease.

2015-10-06 | E-MTAB-3600 | biostudies-arrayexpress

Identification of evolutionary mechanisms of myelomatous effusion by single-cell RNA sequencing

Project description:Myelomatous effusion (ME) is a rare manifestion of extramedullary multiple myeloma (MM) with limited therapeutic options and poor outcomes. To investigate the evolutionary mechanisms of ME, we used single-cell RNA sequencing to assess the transcriptomes of bone marrow, peripheral blood, and pleural effusion/ascites from three patients with ME.

2023-04-26 | GSE230510 | GEO

Single-cell transcriptomic analysis of NK cell dynamics in myeloma patients reveal persistent reduction of cytotoxic NK cells from diagnosis to relapse

Project description:Single-cell transcriptomics was performed to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis (n=19), during treatment (n=21) and at relapse (n=6). The bone marrow of myeloma patients is characterized by a reduction in conventional cytotoxic NK cells that persists throughout treatment. We show in 20% of newly diagnosed myeloma patients that an altered balance between cytotoxic and cytokine-producing NK cells translates into a reduced cytotoxic ability in response to therapeutic antibodies. The relative loss of cytotoxic NK cells persists at relapse and is accompanied by an expansion of IFN-responsive NK cells. These findings reveal previously unappreciated alterations in bone marrow NK cell composition and highlight the importance of understanding the bone marrow immune system in patients receiving immunotherapies.

2023-07-18 | E-MTAB-13157 | biostudies-arrayexpress

IL21R-expressing CD14+CD16+ monocytes expand in multiple myeloma patients leading to increased osteoclasts

Project description:Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes from patients with multiple myeloma, smoldering myeloma or monoclonal gammopathy of undetermined significance. We analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14+ monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis. The number of bone marrow CD14+CD16+ cells was higher in patients with active myeloma than in those with smoldering myeloma or monoclonal gammopathy of undetermined significance. Interestingly, sorted bone marrow CD14+CD16+ cells from myeloma patients were more pro-osteoclastogenic than CD14+CD16-cells in cultures ex vivo Moreover, transcriptional analysis demonstrated that bone marrow CD14+ cells from patients with multiple myeloma (but neither monoclonal gammopathy of undetermined significance nor smoldering myeloma) significantly upregulated genes involved in osteoclast formation, including IL21RIL21R mRNA over-expression by bone marrow CD14+ cells was independent of the presence of interleukin-21. Consistently, interleukin-21 production by T cells as well as levels of interleukin-21 in the bone marrow were not significantly different among monoclonal gammopathies. Thereafter, we showed that IL21R over-expression in CD14+ cells increased osteoclast formation. Consistently, interleukin-21 receptor signaling inhibition by Janex 1 suppressed osteoclast differentiation from bone marrow CD14+ cells of myeloma patients. Our results indicate that bone marrow monocytes from multiple myeloma patients show distinct features compared to those from patients with indolent monoclonal gammopathies, supporting the role of IL21R over-expression by bone marrow CD14+ cells in enhanced osteoclast formation.

2017-04-11 | GSE70345 | GEO

Genome-wide profiling of tumor cells in multiple myeloma

Project description:In multiple myeloma (MM), endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. They share a common bone marrow microenvironment with myeloma tumor cells. CD138+ tumor plasma cells from 12 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression. Tumor cells were derived from single-cell suspensions of bone marrow (BM) aspirates from newly diagnosed MM patients, and RNA was extracted for microarray hybridization.

2011-04-02 | E-GEOD-28327 | biostudies-arrayexpress

Chromothripsis 18 in multiple myeloma patient with rapid extramedullary relapse.

Project description:Retrospective investigation of genetic background of rapid progression of multiple myeloma into extramedullary relapse. Array-CGH showed chromothripsis in chromosome 18, hyperdiploidy, structural copy-number alterations. Utilization of novel NGS leukemia-related gene custom panel revealed patholological mutation in NRAS (c.181C>A; p.Gln61Lys) or variants of unknown significance in TP53, CUX1 and POU4F1.

2017-10-31 | E-MTAB-6033 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data