Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling by array of human CD138 purified bone marrow plasma cells, CD27 memory B-cells, polyclonal plasmablastic cells and human myeloma cell lines

ABSTRACT: Gene expression profiling of CD138 purified bone marrow plasma cells of healthy donors, CD27 memory B-cells, cultured ployclonal plasmablastic cells and cultured human myeloma cell lines. Samples from healthy donors have been re-used from ArrayExpress experiment E-MEXP-2360. Some of the myeloma cell line samples have been re-used from E-TABM-937 and E-TABM-1088.

ORGANISM(S): Homo sapiens

SUBMITTER: Susanne Beck

PROVIDER: E-MTAB-5212 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The role of microRNAs (miRNAs) in multiple myeloma (MM) has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs) profiled on Affymetrix U133A oligonucleotide microarrays and focused on transcripts whose expression varied significantly across the dataset. We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK) whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs by quantitative real-time RT-PCR. There was a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs with the Affymetrix GeneChip human mapping 250K array set indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets, as well as the transcriptional profiles associated with the primary tumors, suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and/or interactions with the bone marrow microenvironment. Our data support the idea that intronic miRNAs and their host genes are regulated dependently, and may contribute to the understanding of their biological roles in cancer. To our knowledge, this is the first evidence of deregulated miRNA expression in MM, providing insights that may lead to the identification of new biomarkers and altered molecular pathways of the disease. Keywords: integrative genomic analysis of miR-335, miR-342, and miR-561 in multiple myeloma This series of microarray experiments contains the genome-wide profiles of 20 HMCLs. 250 nanograms of genomic DNA was processed and, in accordance with the manufacturer's protocols, 90 micrograms of fragmented biotin-labelled DNA were hybridized on GeneChip® Human Mapping 250K NspI Arrays (Affymetrix Inc.). The arrays were scanned using the GeneChip® Scanner 3000 7G. The images were acquired using Affymetrix GeneChip® Operating Software (GCOS version 1.4). Copy number values for individual SNPs were extracted and converted from CEL files into signal intensities using GTYPE 4.1 and Affymetrix Copy Number Analysis Tool (CNAT 4.0.1) softwares. Raw data were extracted using the Hidden Markov Model Genomic Smoothing window was set to 0. After the preprocessing, piecewise constant estimates of the underlying local DNA CN variation was calculated using the DNA copy Bioconductor package, which looks for optimal breakpoints using circular binary segmentation (CBS).

Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients Eight healthy donor and eight myeloma patients were used in the study. Non-expanded natural killer (NK) cells were isolated from PBMCs of healthy donors and myeloma patients. Expanded natural killer (ENK) cells were generated from same set of samples as mentioned in expansion protocol. All ENK and NK cells were used for gene expression profiling.

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Transcription profiling by array of human CD138 purified bone marrow plasma cells, CD27 memory B-cells, polyclonal plasmablastic cells and human myeloma cell lines

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