Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA profiling of peripheral blood mononuclear cells from CLL patients to identify a signature for specific chromasomal abnormalities

ABSTRACT: We studied the value of the microRNAs as a signature for CLL patients with specific chromosomal abnormalities. We identified 32 microRNAs able to discriminate the 11q deletion, 17p deletion, trisomy 12, and 13q deletion and normal karyotype cytogenetic subgroups. The expression values of 9 among the 32 microRNAs (miR-151-3p, miR-34a, miR-29c, miR-29b, miR-155, miR-148a, miR-146a, miR-146b5p and miR-640) were correlated with genes expression data from the same samples to assess their biological impact on CLL. In this study we also found that IGHV unmutated, high expression of ZAP-70 protein and low expression of the miR-223, miR-29c, miR-29b, and miR-181 family were strongly associated with disease progression in CLL cases harboring 17p deletion; whereas in those harboring trisomy 12 only high expression of the miR-181a, among the analyzed parameters, suggested more aggressive disease. Thus, the use of the microRNA-based classifications may yield clinically useful bio-markers of tumor behavior in CLL.

ORGANISM(S): Homo sapiens

SUBMITTER: Cristian Taccioli

PROVIDER: E-TABM-763 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Karyotype-specific microRNA signature in chronic lymphocytic leukemia.

Visone Rosa R Rassenti Laura Z LZ Veronese Angelo A Taccioli Cristian C Costinean Stefan S Aguda Baltazar D BD Volinia Stefano S Ferracin Manuela M Palatini Jeff J Balatti Veronica V Alder Hansjuerg H Negrini Massimo M Kipps Thomas J TJ Croce Carlo M CM

Blood 20090828 18

Chromosomal abnormalities, immunoglobulin heavy chain variable-region (IGHV) gene mutation status, and zeta-associated protein 70 (ZAP-70) expression levels have independent prognostic relevance in chronic lymphocytic leukemia (CLL); however, their concordance is variable. Because deregulation of microRNAs has been linked to disease initiation and progression in CLL, we studied the value of the microRNAs as a signature for CLL patients with specific chromosomal abnormalities. We identified 32 mi ...[more]

PMID: 19717645

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Project description:Distinct genetic abnormalities such as TP53 deletion at 17p13.1, have been identified as having an adverse prognostic relevance in B-cell chronic lymphocytic leukemia (B-CLL). Conventional cytogenetic studies have shown that TP53 deletion in B-CLL is associated predominantly with 17p loss resulting from complex chromosomal rearrangements. We performed genome-wide DNA (SNPs arrays), fluorescence in situ hybridization (FISH) and gene expression profiling (GEP) analyses to investigate the significance of 17p loss in a panel of 71 genetically well-characterized B-CLLs in Binet stage A, 18 of which carried a TP53 monoallelic deletion. Combined SNP arrays and FISH approaches showed 17p loss in all of the TP53-deleted cases, with breakpoints scattered along the 17p11.2 region. Mutations in exons 5 to 9 of TP53 were found in 9/12 deleted samples. GEP of 60 B-CLLs, including 7 patients with 17p loss, identified 40 differentially expressed genes in 17p- versus 17p normal samples, 35 of which were down-regulated in 17p- tumors. The majority (30/35) of these transcripts, including putative tumor suppressor genes, mapped to 17p. Overall, these data indicate that, beside TP53 deletion, the concomitant loss of 17p arm may contribute to the strong negative prognostic impact known to be associated with this lesion in B-CLL. Keywords: transcriptional analysis of B-CLL with 17p loss patients This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 60 newly diagnosed patients (Binet stage A). Peripheral blood mononuclear cells from B-CLL patients were isolated by Ficoll-Hypaque density-gradient centrifugation and the proportion of CD5/CD19/CD23 triple positive B cells in the suspension was determined by direct immunofluorescence performed using a FACS-sort flow cytometer with antibodies to: CD19 FITC/PE, CD23 PE and CD5 Cy-Chrome. If B-CLL cells were less than 90%, T cells, NK cells and monocytes were removed by negative selection using CD3, CD56, CD16, and CD14 monoclonal antibody treatment followed by magnetic beads. 3 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 GeneChip Scanner 3000 7G. The images were acquired using Affymetrix GeneChipÂ® Operating Software (GCOS version 1.4) 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

MicroRNA profiling of peripheral blood mononuclear cells from CLL patients to identify a signature for specific chromasomal abnormalities

Publications

Karyotype-specific microRNA signature in chronic lymphocytic leukemia.

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