Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human plasma cells from patients with monoclonal gammopathy of undetermined significance, multiple myeloma or plasma-cell leukaemia

ABSTRACT: This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 7 monoclonal gammopathy of undetermined significance (MGUS), 39 newly diagnosed multiple myeloma (MM) and 6 plasma-cell leukaemia (PCL) patients. PCs were purified from bone marrow Seriess, after red blood cell lysis with 0.86% ammonium chloride, using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5 micrograms of total RNA was processed and hybridized to the Affymetrix HG-U133A chip following the manufacturer's instructions. After scanning, the images were processed using Affymetrix MicroArray Suite (MAS) 5.0 software to generate gene expression intensity values. Arrays normalization was performed using MAS 5.0 global scaling" procedure, which normalizes the signals of different experiments to the same target intensity (TGT=100).

ORGANISM(S): Homo sapiens

DISEASE(S): monoclonal gammopathy of undetermined significance (MGUS)

SUBMITTER: Antonino Neri

PROVIDER: E-GEOD-2113 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma.

Mattioli Michela M Agnelli Luca L Fabris Sonia S Baldini Luca L Morabito Fortunato F Bicciato Silvio S Verdelli Donata D Intini Daniela D Nobili Lucia L Cro Lilla L Pruneri Giancarlo G Callea Vincenzo V Stelitano Caterina C Maiolo Anna Teresa AT Lombardi Luigia L Neri Antonino A

Oncogene 20050401 15

Multiple myeloma (MM) is the most common form of plasma cell dyscrasia, characterized by a marked heterogeneity of genetic lesions and clinical course. It may develop from a premalignant condition (monoclonal gammopathy of undetermined significance, MGUS) or progress from intramedullary to extramedullary forms (plasma cell leukemia, PCL). To provide insights into the molecular characterization of plasma cell dyscrasias and to investigate the contribution of specific genetic lesions to the biolog ...[more]

PMID: 15735737

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Project description:Platelet concentrates (PCs) represent a blood transfusion product with a major concern for safety as their storage temperature (20-24ºC) allows bacterial growth, and their maximum storage time period (less than a week) precludes complete microbiological testing. Pathogen inactivation technologies (PITs) provide an additional layer of safety to the blood transfusion products from known and unknown pathogens (such as bacteria, viruses and parasites). In this context, PITs (such as Mirasol Pathogen Reduction Technology -PRT-) have been developed and are implemented in many countries. However, several studies have shown in vitro that Mirasol PRT induces a certain level of platelet shape change, hyperactivation, basal degranulation and increased oxidative damage during storage. It has been suggested that Mirasol PRT might accelerate what has been described as the platelet storage lesion (PSL), but supportive molecular signatures have not been obtained. We aimed at dissecting the influence of both variables, i.e. Mirasol PRT and storage time, at the proteome level. We present comprehensive proteomics data analysis of Control PCs and PCs treated with Mirasol PRT at storage days 2, 6 and 8. Our workflow was set to perform proteomics analysis using a gel-free and label-free quantification (LFQ) approach. Semi-quantification was based on LFQ signal intensities of identified proteins using MaxQuant/Perseus software platform. We identified marginal differences between Mirasol PRT and control PCs during storage. However, those significant changes at the proteome level were specifically related to the functional aspects previously described to affect platelets upon Mirasol PRT, and in addition, the effect of Mirasol PRT on the platelet proteome appeared not to be exclusively due to an accelerated or enhanced PSL. In summary, semi-quantitative proteomics allows to discern between proteome changes due to Mirasol PRT or PSL, and proves to be a methodology suitable to phenotype platelets in an unbiased manner, in various physiological contexts.

Project description:To date, little evidence of miRNA expression/deregulation in multiple myeloma (MM) has been reported. To characterize miRNA expression profiling of MM plasma cells (PCs) and integrate miRNA expression data with other molecular features of MM patients, global miRNA expression profiles were generated for PCs isolated from BM biopsies of 38 newly diagnosed MM, 2 plasma cell leukemia patients, and 3 healthy donors; the samples were also profiled for global gene expression, and nineteen of them underwent genome-wide DNA analysis using high-density SNP-microarrays. Differential miRNA expression patterns were mainly identified in association with the major IGH translocations: in particular, t(4;14) showed specific over-expression of let-7e, miR-125a-5p and miR-99b belonging to a cluster at 19q13.33. The occurrence of other lesions, such as 1q gain, 13q and 17p deletions, and hyperdiploidy, was less well characterized by specific miRNA signatures. Genome-wide analysis showed that some allelic imbalances led to the significantly altered expression of miRNAs located in the involved regions, such as let-7b at 22q13.31 loss and miR-142-3p at 17q22 gain. The integrative analysis based on computational target prediction, miRNA and mRNA profiling defined a network of putative functional miRNA-target regulatory relations supported by expression data. This series of microarray experiments contains the microRNA profiles of purified plasma cells (PCs) obtained from 3 normal donor (N), 38 multiple myeloma (MM) and 2 plasma cell leukemia (PCL) at diagnosis. PCs were purified from bone marrow specimens after red blood cell lysis with 0.86% ammonium chloride using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was >90% in all cases. 500 nanograms of total RNA was processed in accordance with the manufacturer's protocols (Agilent Technologies) to generate Cy3-labeled RNA which were purified on chromatography columns (Micro Biospin 6, Bio-Rad, Hercules, CA) and hybridized on an Agilent microarray (G4470B) at 55Â°C for 17 hr in a rotating oven. Images at 5 um resolution were generated using an Agilent scanner G2505B. The Feature Extraction 9.5 software (Agilent Technologies) was used to obtain the raw microarray data. The human miRNAs included in the platform were annotated according to Sanger miRBase Release 12.0. After discarding non-human miRNAs, the data were normalized using the Aroma Light package for Bioconductor. To overcome scaling biases due to background subtraction, the data were converted to obtain positive values throughout the dataset, at a minimum value of 1. The global gene expression raw data used in this study was originally deposited as GSE13591 and renormalized for this study. The genome wide profile (DNA) analysis was originally deposited as GSE16121.

Project description:Multiple myeloma (MM) is characterized by marked genomic instability. Beyond structural rearrangements, a relevant role in its biology is represented by allelic imbalances leading to significant variations in ploidy status. To better elucidate the genomic complexity of MM, we analyzed a panel of 45 patients using combined FISH and microarray approaches. Using a self-developed procedure to infer exact local copy numbers for each sample, we identified a significant fraction of patients showing marked aneuploidy. A conventional clustering analysis showed that aneuploidy, chromosome 1 alterations, hyperdiploidy and recursive deletions at 1p and chromosomes 13, 14 and 22 were the main aberrations driving samples grouping. Then, we integrated mapping information with gene and microRNAs expression profiles: a multiclass analysis of the identified clusters showed a marked gene-dosage effect, particularly concerning 1q transcripts, also confirmed by correlating gene expression levels and local copy number alterations. A wide dosage effect affected also microRNAs, indicating that structural abnormalities in MM closely reflect in their expression imbalances. Finally, we identified several loci in which genes and microRNAs expression correlated with loss-of-heterozygosity occurrence. Our results provide insights into the composite network linking genome structure and gene/microRNA transcriptional features in MM. Experiment Overall Design: This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 4 normal donor (N), 11 monoclonal gammopathy of undetermined significance (MGUS), 133 multiple myeloma (MM) and 9 plasma cell leukemia (PCL) at diagnosis. PCs were purified from bone marrow specimens, after red blood cell lysis with 0.86% ammonium chloride, using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5 micrograms of total RNA was processed and, in accordance with the manufacturer's protocols, 15 micrograms of fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133A Arrays (Affymetrix Inc.). The arrays were scanned using the Agilent GeneChip Scanner G2500A. The images were acquired using Affymetrix MicroArray Suite (MAS) 5.0 software and the probe level data converted to expression values using the Bioconductor function for the Robust Multi-Array average (RMA) procedure (Irizarry et al, 2003), in which perfect match intensities are background adjusted, quantile-quantile normalised and log2 transformed.

Project description:Karyotypic instability, including numerical and structural chromosomal aberrations, represents a distinct feature of multiple myeloma (MM). 40-50% of patients displayed hyperdiploidy, defined by recurrent trisomies of non-random chromosomes. To characterize hyperdiploid (H) and nonhyperdiploid (NH) MM molecularly, we analyzed the gene expression profiles of 66 primary tumors, and used FISH to investigate the major chromosomal alterations. The differential expression of 225 genes mainly involved in protein biosynthesis, transcriptional machinery and oxidative phosphorylation distinguished the 28 H-MM from the 38 NH-MM cases. The 204 upregulated genes in H-MM mapped mainly to the chromosomes involved in hyperdiploidy, and the29% up-regulated genes in NH-MM mapped to 16q. The identified transcriptional fingerprint was robustly validated on a publicly available gene expression dataset of 64 MM cases; and the global expression modulation of regions on the chromosomes involved in hyperdiploidy was verified using a self-developed non-parametric statistical method. We showed that H-MM could be further divided into two distinct molecular and transcriptional entities, characterized by the presence of trisomy 11 and 1q-extracopies/chromosome 13 deletion, respectively. Our data reinforce the importance of combining molecular cytogenetics and gene expression profiling to define a genomic framework for the study of MM pathogenesis and clinical management. Experiment Overall Design: This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 102 newly diagnosed multiple myeloma (MM). PCs were purified from bone marrow specimens, after red blood cell lysis with 0.86% ammonium chloride, using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5 micrograms of total RNA was processed and, in accordance with the manufacturer's protocols, 15 micrograms of fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133A Arrays (Affymetrix Inc.). The arrays were scanned using the Agilent GeneChip Scanner G2500A. The images were acquired using Affymetrix MicroArray Suite (MAS) 5.0 software and the probe level data converted to expression values using the Bioconductor function for the Robust Multi-Array average (RMA) procedure (Irizarry et al, 2003), in which perfect match intensities are background adjusted and quantile-quantile normalised.

Project description:Background and objective: The chromosome 13 deletion (del(13)) represents one of the most frequent chromosomal alterations in multiple myeloma (MM). del(13) is associated with an unfavorable prognosis, although there is an increasing agreement that its prognostic relevance has to be related to the ploidy status and the presence of different chromosomal translocations. This study is aimed at providing a comprehensive analysis of the transcriptional features of del(13) in MM. Design and methods: Highly purified plasma cells from 80 newly diagnosed MM patients were characterized by means of FISH and high-density oligonucleotide microarray for gene expression profiling and chromosomal alterations. Results: We identified 67 differentially expressed genes in the del(13)+ and del(13)- groups, all of which downregulated in the del(13)+ cases: 44 mapped along the whole chromosome 13, seven on chromosome 11 and three on chromosome 19. Functional analyses of the selected genes indicated their involvement in protein biosynthesis, ubiquitination and transcriptional regulation. An integrative genomic approach based on regional analyses of the gene expression data identified distinct chromosomal regions whose global expression modulation could differentiate del(13)+, in particular the upregulation of 1q21-1q42 and the downregulation of 19p and almost the entire chromosome 11. FISH analyses confirmed the close relationship between del(13)+ and the presence of extracopies of 1q21-1q42 (P=6x10-4) or the absence of chromosome 11 and 19 trisomy (P=5x10-4). Interpretation and conclusions: Our results indicate that distinct types of chromosomal aberrations are closely related to the transcriptional profiles of del(13)+, suggesting that the contribution of del(13) on the malignancy should be considered together with associated abnormalities. Experiment Overall Design: This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 90 newly diagnosed multiple myeloma (MM). PCs were purified from bone marrow specimens, after red blood cell lysis with 0.86% ammonium chloride, using CD138 immunomagnetic microbeads. The purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5 micrograms of total RNA was processed and, in accordance with the manufacturer's protocols, 15 micrograms of fragmented biotin-labelled cRNA were hybridized on GeneChip Human Genome U133A Arrays (Affymetrix Inc.). The arrays were scanned using the Agilent GeneChip Scanner G2500A. The images were acquired using Affymetrix MicroArray Suite (MAS) 5.0 software and the probe level data converted to expression values using the Bioconductor function for the Robust Multi-Array average (RMA) procedure (Irizarry et al, 2003), in which perfect match intensities are background adjusted and quantile-quantile normalised.

Dataset Information

Transcription profiling of human plasma cells from patients with monoclonal gammopathy of undetermined significance, multiple myeloma or plasma-cell leukaemia

Publications

Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma.

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