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Gene expression study in CLL of B-cell receptor triggering

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: daniela marconi

PROVIDER: E-GEOD-52776 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression study in CLL of B-cell receptor triggering (mRNA Study)

Project description:The B-cell receptor (BCR) plays an important role in pathogenesis and progression of chronic lymphocytic leukemia (CLL). We investigated the BCR triggering-dependent mRNA modulation by stimulating CLL cells with immobilized anti-IgM. miRome of immobilized anti-IgM stimulated CLL cells (n=16) identified a substantial upregulation of miR-132 in both unmutated (UM) and mutated (M) IGHV subgroups. A parallel gene expression profile and an in-silico analysis to identify miR-132 target genesÂ¸ allowed us to focus on SIRT1, that encodes for a histone deacetylase targeting several proteins including TP53. We defined a reduction of SIRT1 protein levels upon immobilized anti-IgM stimulation (P=0.001), and a concomitant increase in TP53 acetylation (P=0.0072). The TP53 target gene CDKN1A was consistently up-regulated in immobilized anti-IgM stimulated CLL cells. Of note, the miR-132 constitutive expression levels in CLL cases (n=134) were of similar magnitude of those obtained in in vitro immobilized anti-IgM stimulated CLL cells. Additionally, high miR-132 expression levels retained a favorable prognostic impact in M (P=0.005), but not in UM CLL patients (P=0.968). The described miR-132/SIRT1/TP53 axis, sequentially characterized by BCR triggering, miR-132 up-regulation, SIRT1 down-regulation and TP53 acetylation, should be considered in the light of emerging drugs targeting the BCR pathway in CLL. Investigated the BCR triggering-dependent gene expression modulation by stimulating CLL cells with immobilized anti-IgM.

2014-01-01 | E-GEOD-52774 | biostudies-arrayexpress

Gene expression study in CLL of B-cell receptor triggering (miRNA study)

Project description:The B-cell receptor (BCR) plays an important role in pathogenesis and progression of chronic lymphocytic leukemia (CLL). We investigated the BCR triggering-dependent microRNA modulation by stimulating CLL cells with immobilized anti-IgM. miRome of immobilized anti-IgM stimulated CLL cells (n=16) identified a substantial upregulation of miR-132 in both unmutated (UM) and mutated (M) IGHV subgroups. A parallel gene expression profile and an in-silico analysis to identify miR-132 target genes¸ allowed us to focus on SIRT1, that encodes for a histone deacetylase targeting several proteins including TP53. We defined a reduction of SIRT1 protein levels upon immobilized anti-IgM stimulation (P=0.001), and a concomitant increase in TP53 acetylation (P=0.0072). The TP53 target gene CDKN1A was consistently up-regulated in immobilized anti-IgM stimulated CLL cells. Of note, the miR-132 constitutive expression levels in CLL cases (n=134) were of similar magnitude of those obtained in in vitro immobilized anti-IgM stimulated CLL cells. Additionally, high miR-132 expression levels retained a favorable prognostic impact in M (P=0.005), but not in UM CLL patients (P=0.968). The described miR-132/SIRT1/TP53 axis, sequentially characterized by BCR triggering, miR-132 up-regulation, SIRT1 down-regulation and TP53 acetylation, should be considered in the light of emerging drugs targeting the BCR pathway in CLL. investigated the BCR triggering-dependent gene expression modulation by stimulating CLL cells with immobilized anti-IgM.

2014-01-01 | E-GEOD-52775 | biostudies-arrayexpress

miRNA and mRNA expression profile of CLL cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2011-06-30 | E-GEOD-30107 | biostudies-arrayexpress

miRNA expression profile of unmutated and mutated CLL cells

Project description:The aim is to identify the differential miRNA expression profile of B-CLL stimulated with different type of stimulation CPG One color design, 36 samples, Two-condition experiment, CPG-stimulated B-CLL unmutated and mutated vs. Unstimulated B-CLL unmutated and mutated. Biological replicates: 18 unstimulated replicates, 18 CPG-stimulated replicates.

2011-06-30 | E-GEOD-30106 | biostudies-arrayexpress

CPG stimulation for Gene Expression of unmutated B-CLL

Project description:The aim is to identify the differential gene expression profile of unmutated B-CLL stimulated with CPG. Two-condition experiment, CPG-stimulated B-CLL unmutated vs. Unstimulated B-CLL unmutated . Biological replicates: 9 unstimulated replicates, 9 CPG-stimulated replicates. Reference design;

2011-06-30 | E-GEOD-30105 | biostudies-arrayexpress

CPG stimulation for Gene Expression of mutated B-CLL

Project description:The aim is to identify the differential gene expression profile of mutated B-CLL stimulated with CPG Two-condition experiment, CPG-stimulated B-CLL mutated vs. Unstimulated B-CLL mutated . Biological replicates: 8 unstimulated replicates, 8 CPG-stimulated replicates. Reference design;

2011-08-17 | E-GEOD-31360 | biostudies-arrayexpress

Increased chronic lymphocytic leukemia proliferation upon IgM stimulation is sustained by the upregulation of miR-132 and miR-212

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-02-10 | E-GEOD-49697 | biostudies-arrayexpress

Increased CLL Proliferation upon IgM stimulation is Sustained by the Up-regulation of miR-132 and miR-212: a Combined miRNA and Gene Expression Profiling Analysis and Correlation with Disease Progression [miRNA expression]

Project description:In order to investigate a potential involvement of miRNAs in BCR stimulation, in the present work we first evaluated their expression following IgM cross-linking in CLL cells, as well as in healthy B lymphocytes. Next, to infer putative miRNA targeting networks, we combined miRNA profiling results with gene expression and functional analyses miRNA expression profiling analysis by microarray analysis of CLL samples and pools of CD19+ cells derived from healthy donors.

2015-02-10 | E-GEOD-49696 | biostudies-arrayexpress

Project description:In order to investigate a potential involvement of miRNAs in BCR stimulation, in the present work we first evaluated their expression following IgM cross-linking in CLL cells, as well as in healthy B lymphocytes. Next, to infer putative miRNA targeting networks, we combined miRNA profiling results with gene expression and functional analyses Gene expression profiling analysis by microarray analysis of CLL samples.

2015-02-10 | E-GEOD-49695 | biostudies-arrayexpress

A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions

Project description:The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. To characterize the transcriptional changes of early breast neoplasia, we sequenced 3'- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. 3SEQ was performed on 72 FFPE human breast samples from 25 patients: 24 normal, 25 early neoplasia, 9 carcinoma in situ, and 14 invasive cancer

2014-05-04 | E-GEOD-47462 | biostudies-arrayexpress

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