Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

A Pathobiological Role of the Insulin Receptor in CLL.

ABSTRACT: Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Results: We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (~10-fold higher mean levels than other genomic categories) was confirmed by Q-PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through FACS, compared with measurements in normal CD19+ B-cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels. We have employed integrated genomic profiling approaches upon CLL cases with and without del11q to identify 11q-relevant genes. Included are 10 primary human cases with del11q and 9 cases without del11q

ORGANISM(S): Homo sapiens

SUBMITTER: Sami Malek

PROVIDER: E-GEOD-26526 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A pathobiological role of the insulin receptor in chronic lymphocytic leukemia.

Saiya-Cork Kamlai K Collins Roxane R Parkin Brian B Ouillette Peter P Kuizon Erlene E Kujawski Lisa L Erba Harry H Campagnaro Erica E Shedden Kerby K Kaminski Mark M Malek Sami N SN

Clinical cancer research : an official journal of the American Association for Cancer Research 20110209 9

<h4>Purpose</h4>The chromosomal deletion 11q affects biology and clinical outcome in chronic lymphocytic leukemia (CLL) but del11q-deregulated genes remain incompletely characterized.<h4>Experimental design</h4>We have employed integrated genomic profiling approaches on CLL cases with and without del11q to identify 11q-relevant genes.<h4>Results</h4>We have identified differential expression of the insulin receptor (INSR) in CLL, including high-level INSR expression in the majority of CLL with d ...[more]

PMID: 21307146

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Project description:Prospective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. Trisomy 12, 11q- and 17p- abnormalities were scanty and of no predictive value in both conditions. Notably, gene and miRNA expression profiling showed no significant differences between cMBL and Rai0-CLL. Furthermore, similar gene and miRNA expression signatures were found in cMBL and Rai0-CLL according to the IGHV gene mutational status: that is, unmutated cases had different signatures from mutated cases, irrespectively of the cMBL or CLL condition. Overall, our study based on a prospective series of patients indicates that no major biological differences exist in cMBL compared to Rai0-CLL, suggesting that this two entities mainly differ for the initial size of the monoclonal cell population which may reflect in the longer time for clonal expansion. This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 160 patients (Binet stage A) including 45 cMBL and 115 Rai0-CLL. Peripheral blood mononuclear cells from CLL patients were isolated by Ficoll-Hypaque (Seromed, Biochrom KG, Berlin, Germany) density-gradient centrifugation. For gene and miRNA expression profiling experiments CLL cells were enriched by negative selection with the EasySep-Human B cell enrichment kit without CD43 depletion (Stem Cell Technologies) using the fully automated protocol of immunomagnetic cell separation with RoboSepTM (Stem Cell Technologies).

Dataset Information

A Pathobiological Role of the Insulin Receptor in CLL.

Publications

A pathobiological role of the insulin receptor in chronic lymphocytic leukemia.

Similar Datasets

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