Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA149407 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glucocorticoids are part of the therapeutic armamentarium of chronic lymphocytic leukemia where it has been suggested that cells with unmutated IGHV genes exhibit higher sensitivity. The mechanisms by which glucorticoids are active in CLL are not well elucidated. We used microarrays to detail the global programme of gene expression underlying dexamethasone differential activity according to the prognostic subgroups mutated IGHV genes / low ZAP-70 expression and unmutated IGHV genes / high ZAP-70 expression. We aimed to ascertain the molecular mechanisms that are influencing the diffferential response to this drug. Peripheral blood mononuclear cells from chronic lymphocytic leukemia patients were obtained. Samples were split in two for control and incubation with dexamethasone for 6 hours. RNA was extracted and processed for further hybridization on Affymetrix microarrays.
2012-12-04 | E-GEOD-33135 | biostudies-arrayexpress
Project description:Glucocorticoids are part of the therapeutic armamentarium of chronic lymphocytic leukemia where it has been suggested that cells with unmutated IGHV genes exhibit higher sensitivity. The mechanisms by which glucorticoids are active in CLL are not well elucidated. We used microarrays to detail the global programme of gene expression underlying dexamethasone differential activity according to the prognostic subgroups mutated IGHV genes / low ZAP-70 expression and unmutated IGHV genes / high ZAP-70 expression. We aimed to ascertain the molecular mechanisms that are influencing the diffferential response to this drug.
2012-12-04 | GSE33135 | GEO
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).
2013-08-30 | E-GEOD-40570 | biostudies-arrayexpress
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.
2013-08-30 | GSE40570 | GEO
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.
2013-08-30 | GSE40533 | GEO
Project description:B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of ZAP-70 and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-), intermediate (discordant expression of ZAP-70 and CD38) and poor (ZAP-70+CD38+) prognosis. In an attempt to identify a molecular basis that may underly this diverse clinical behaviour DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. We used microarrays to detail the global programme of gene expression distinguising B-CLL from patient with good (samples 1 to 8) and poor prognosis (sample 9 to 16) and identified distinct classes of up- and down-regulated genes. Keywords: Disease progression
2006-09-22 | GSE4392 | GEO
Project description:We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia-cell-expression levels that varied among patients. CLL cells that expressed ZAP-70 or that used unmutated IGHV each had a median expression-level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3M-bM-^@M-^Y UTRs having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that may enhance B-cell receptor (BCR) signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 levels was a significant independent predictor of longer treatment-free-survival (TFS) or overall survival (OS), whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for OS. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor (BCR), thereby possibly accounting for the noted association of expression of miR-150 and disease outcome. We performed gene expression analysis on isolated leukemia cells from 100 CLL patients using the Affymetrix HG-U133 Plus 2 platform. Array data was processed by dChip software (http://www.dchip.org). No techinical replicates were performed.
2014-08-04 | E-GEOD-49896 | biostudies-arrayexpress
Project description:ARSD expression correlates with IgVH mutational status, ZAP-70 and disease progression in chronic lymphocytic leukemia
| PRJNA138851 | ENA
Project description:We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia-cell-expression levels that varied among patients. CLL cells that expressed ZAP-70 or that used unmutated IGHV each had a median expression-level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3’ UTRs having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that may enhance B-cell receptor (BCR) signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 levels was a significant independent predictor of longer treatment-free-survival (TFS) or overall survival (OS), whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for OS. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor (BCR), thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.
2014-08-04 | GSE49896 | GEO
Project description:B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of ZAP-70 and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-), intermediate (discordant expression of ZAP-70 and CD38) and poor (ZAP-70+CD38+) prognosis. In an attempt to identify a molecular basis that may underly this diverse clinical behaviour DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. We used microarrays to detail the global programme of gene expression distinguising B-CLL from patient with good (samples 1 to 8) and poor prognosis (sample 9 to 16) and identified distinct classes of up- and down-regulated genes. Experiment Overall Design: To compare the transcriptosomes of good prognosis CLL cases (ZAP-70-CD38-) to poor prognosis cases (ZAP-70+CD38+), we purified CD19+ cells from peripheral blood samples by immunomagnetic isolation using MidiMacs, resulting in >95% purity of leukemic cells as detected by FACS analysis of CD19+CD5+ cells. The leukemic cells were freshly purified from untreated patients and RNA was directly isolated from fresh cells without further ex vivo treatment of the cells. Eight immunomagnetically purified peripheral blood derived ZAP-70+CD38+ CLL cases were compared with eight ZAP-70-CD38- B-CLL cases.
2009-04-23 | E-GEOD-4392 | biostudies-arrayexpress