ATAC Sequencing of 4 CLL patient samples
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ABSTRACT:
PROVIDER: EGAS00001006206 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Chronic lymphocytic leukemia shows a variable clinical course which is associated with distinct alterations such as chromosomal aberrations, gene mutations or IGHV mutation status. Refining biologic categories may help to improve clinical management with available and future treatment approaches. We used Affymetrix Exon 1.0 ST microarrays to investigate differences in CLL biology.
2021-06-30 | GSE126595 | GEO
Project description:Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are only partially known. This is in part due to a scarcity of information on the proteome of CLL. We profiled the proteome of 117 CLL samples with data-independent acquisition mass spectrometry (DIA-MS) and integrated the results with genomic, transcriptomic, functional data and clinical outcome. We found trisomy 12 and IGHV to be major determinants of proteome variation in CLL (1055 and 542 differential proteins FDR of 5%). Trisomy 12 was associated with limited protein abundance buffering. Protein complex analyses detected functional units involved in BCR/PI3K/AKT signaling in CLL with trisomy 12. We associated protein expression with response to anticancer drugs, and STAT2 protein expression emerged as a biomarker for the prediction of response to kinase inhibitors including BTK and MEK inhibitors. STAT2 protein levels were determined by gene dosage (trisomy 12), stabilization in a protein complex and linked to interferon signaling in CLL. This study highlights the emerging importance of protein abundance profiling in CLL biology.
2021-09-24 | PXD022198 | Pride
Project description:In the present study, the methylation profiling (MeDIP) was carried out in 14 treatment-naive, early stage (Rai stage 0-2) CLL patients and pooled 19+ normal controls. To find an association of methylation with IGHV mutation status, CLL patients were further segregated into IGHV unmutated (n=9) and IGHV mutated (n=5) subgroups. The methylation signature obtained for CLL versus nornal controls and; unmutated versus mutated CLL was integrated with gene expression profile of these patients and the results were correlated with clinical outcome.
2017-05-29 | GSE81936 | GEO
Project description:We compared gene expression profiles of CLL patients with and without MYD88 L265P mutations, taking into consideration IGHV mutation status.
2015-06-01 | GSE69034 | GEO
Project description:We have performed a comprehensive proteomic analysis of clinical patient samples of chronic lymphocytic leukemia (CLL) alongside genome-, transcriptome- and ex-vivo drug response profiling. Trisomy 12 and IGHV mutation status had the strongest impact on the proteome and transcriptome; and SF3B1 mutations preferentially affected the proteome. Unsupervised clustering of the proteome data partitioned CLL patients into six protein based subgroups (PG) with contrasting clinical behavior. PG1-4 could be explained by the impact of trisomy 12 and IGHV mutation status on protein abundances and another subgroup (PG6), was enriched for TP53 mutations. In addition we uncovered a new subgroup (PG5) only detectable from the proteome, characterized by low expression of central B-cell receptor proteins, altered splicing, metabolic reprogramming and increased sensitivity to proteasomal inhibition.
2024-06-21 | PXD017453 | Pride
Project description:We have performed a comprehensive proteomic analysis of clinical patient samples of chronic lymphocytic leukemia (CLL) alongside genome-, transcriptome- and ex-vivo drug response profiling. Trisomy 12 and IGHV mutation status had the strongest impact on the proteome and transcriptome; and SF3B1 mutations preferentially affected the proteome. Unsupervised clustering of the proteome data partitioned CLL patients into six protein based subgroups (PG) with contrasting clinical behavior. PG1-4 could be explained by the impact of trisomy 12 and IGHV mutation status on protein abundances and another subgroup (PG6), was enriched for TP53 mutations. In addition we uncovered a new subgroup (PG5) only detectable from the proteome, characterized by low expression of central B-cell receptor proteins, altered splicing, metabolic reprogramming and increased sensitivity to proteasomal inhibition. https://www.ebi.ac.uk/pride/archive/projects/PXD024544
2022-10-17 | PXD028936 | Pride
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: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:Stabilizing mutations of NOTCH1 have been identified in about 10% of chronic lymphocytic leukemia (CLL) cases at diagnosis, with a higher frequency in unmutated IGHV (IGHV-UM) CLL, chemorefractory CLL and CLL in advanced disease phases. Clinically, the presence of NOTCH1 mutations is an independent predictor of overall survival in CLL and associates with resistance to anti-Cd20 immunotherapy. The Gene Expression Profile was generated to identify the peculiar molecular signatures of NOTCH1 mutated CLL in the context of IGHV-UM CLL.
2016-03-01 | GSE75122 | GEO
Project description:Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are only partially known. This is in part due to missing information on the proteome of CLL. We profiled the proteome of 49 diverse CLL samples with data-independent acquisition mass spectrometry (DIA-MS) and related the results to genomic, functional and clinical differences. We found trisomy 12 and IGHV to be major determinants of proteome variation in CLL (1073 and 512 differential proteins). In contrast to reports in other biological systems, the disease driver trisomy 12 was associated with limited protein buffering, a finding that suggests the biological relevance of proteins encoded by chromosome 12 for CLL biology. Protein complex analyses detected functional units involved in BCR/PI3K/AKT signaling in CLL with trisomy 12. We identified the transcription factor complex of STAT1/STAT2 to be up-regulated in IGHV unmutated CLL. We tested the functional relevance of protein expression for associations with response to anticancer drugs, and STAT2 protein expression emerged as a biomarker for the prediction of response to kinase inhibitors including BTK and MEK inhibitors. This study highlights the emerging importance of protein abundance profiling in cancer research and identifies STAT2 protein levels as new key factor in CLL biology.
2021-09-27 | PXD022216 | Pride