DNA methylation arrays of thirty-eight basal tumour samples from CLL patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dean Bryant
PROVIDER: E-MTAB-12018 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:RNAseq of chronic lymphocytic leukaemia (CLL) subsets comprising of Unmutated CLL and Mutated CLL. Mutated CLL cases were further subdivided based on B cell receptor signalling capacity.
2023-05-11 | E-MTAB-12023 | biostudies-arrayexpress
Project description:miRNAseq of chronic lymphocytic leukaemia (CLL) subsets comprising of Unmutated CLL and Mutated CLL. Mutated CLL cases were further subdivided based on B cell receptor signalling capacity.
2023-05-11 | E-MTAB-12017 | biostudies-arrayexpress
Project description:In this study we compared the miRNA expression profile of 217 CLL cases versus various normal B cell subpopulations in the attempt of finding the normal cell subset most similar to CLL cells and gain information on possible miRNA deregulations. Our analyses indicated that CLL cells exhibited a miRNA expression pattern close to memory and marginal zone-like B cells. Conversely, tonsil GC and CD19+ peripheral blood B cells appeared only distantly related to CLL. Memory and marginal zone B cells were used as reference to identify differentially expressed miRNAs in CLL, which included miR-193b, miR-33b*, miR-365, miR-181b and miR-196a/b among the down-regulated and miR-23a/b, miR-26a, miR-130a, miR-532 (5p and 3p) among the up-regulated miRNAs. We also investigated differences of miRNA expression related to the IGHV somatic mutation status and to deletions at 13q, 11q and 17p or trisomy 12. Little differences were detected between unmutated (UM) versus mutated (M) CLLs, although miR-29c, miR-29c* and miR-146b were strongly down-modulated in the UM-CLL subgroup. Each of the cytogenetic classes of CLL was characterized by uniquely abnormally expressed miRNAs. Deletion at 13q displayed a reduced expression of miR-16, more evident if the deletion was biallelic. Deletion of 17p was characterized by the strong reduction of miR-34a expression and up-regulation of miR-96. Deletion at 11q was characterized by the up-regulation of miR-338-3p and miR-769-5p. Trisomy 12 was characterized by a strong down-regulation of miR-483-5p.
2014-03-01 | E-MTAB-1454 | biostudies-arrayexpress
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
Project description:The cellular origin of chronic lymphocytic leukemia (CLL) is debated. Transcriptome analysis of CLL and normal peripheral blood and splenic B cell subsets displayed highest similarity of CLL to mature CD5+ B cells. We identified a distinct CD5+CD27+ post-germinal center B cell subset, and revealed that immunoglobulin V gene mutated CLL are more similar to mutated CD5+ B cells, whereas unmutated CLL are more related to unmutated CD5+ B cells. Stereotyped immunoglobulin V gene rearrangements were significantly enriched among CD5+ B cells, providing further genetic evidence for a derivation of CLL from CD5+ B cells. Moreover, we identified deregulated expression patterns providing novel insights into the pathophysiology of CLL, including downregulation of EBF1 and KLF family members. Transcriptome profiling of CLL and healthy human blood and splenic mature B cell subsets. Identification of deregulated transcription patterns with implications on CLL pathobiology. Human mature B cell subsets and CLL with mutated (mCLL) and unmutated V gene status (uCLL) were purified from peripheral blood and spleen. Samples of 5 to 7 donors each were collected and processed in three batches in a two rounded in vitro transcription protocol. Retrieved data were batch corrected and subjected to analysis. Human mature CD5+ B cell subsets and CLL with mutated (mCLL) and unmutated V gene status (uCLL) were purified from peripheral blood.
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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:Methylation Profiling of IGHV Unmutated vs mutated CLL
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Project description:The mutational status of the immunoglobulin heavy chain variable region (IGHV) defines two clinically distinct forms of chronic lymphocytic leukemia (CLL) known as mutated (M-CLL) and un-mutated (UM-CLL). To elucidate the molecular mechanisms underlying the adverse clinical outcome associated with UM-CLL, total proteomes from 9 UM-CLL and 9 M-CLL samples were analysed by isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. Unsupervised clustering, based on the expression of 3521 identified proteins, separated CLL samples into two groups corresponding to IGHV mutational status. Computational analysis showed that 43 cell migration/adhesion pathways were significantly enriched by 39 differentially expressed proteins, 35 of which were expressed at significantly lower levels in UM-CLL samples. Furthermore, UM-CLL cells under-expressed proteins associated with cytoskeletal remodelling and over-expressed proteins associated with transcriptional and translational activity. Taken together, our findings indicated that UM-CLL cells are less migratory and more adhesive than M-CLL cells, resulting in their retention in lymph nodes where they are exposed to proliferative stimuli. In keeping with this hypothesis, analysis of an extended cohort of 120 CLL patients revealed a strong and specific association between UM-CLL and lymphadenopathy. Our study illustrates the potential of total proteome analysis to elucidate pathogenetic mechanisms in cancer.
2016-06-27 | PXD001516 | Pride
Project description:The mutational status of the immunoglobulin heavy chain variable region (IGHV) defines two clinically distinct forms of chronic lymphocytic leukemia (CLL) known as mutated (M-CLL) and un-mutated (UM-CLL). To elucidate the molecular mechanisms underlying the adverse clinical outcome associated with UM-CLL, total proteomes from 9 UM-CLL and 9 M-CLL samples were analysed by isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. Unsupervised clustering, based on the expression of 3521 identified proteins, separated CLL samples into two groups corresponding to IGHV mutational status. Computational analysis showed that 43 cell migration/adhesion pathways were significantly enriched by 39 differentially expressed proteins, 35 of which were expressed at significantly lower levels in UM-CLL samples. Furthermore, UM-CLL cells under-expressed proteins associated with cytoskeletal remodelling and over-expressed proteins associated with transcriptional and translational activity. Taken together, our findings indicated that UM-CLL cells are less migratory and more adhesive than M-CLL cells, resulting in their retention in lymph nodes where they are exposed to proliferative stimuli. In keeping with this hypothesis, analysis of an extended cohort of 120 CLL patients revealed a strong and specific association between UM-CLL and lymphadenopathy. Our study illustrates the potential of total proteome analysis to elucidate pathogenetic mechanisms in cancer.
2016-06-27 | PXD001512 | Pride
Project description:The mutational status of the immunoglobulin heavy chain variable region (IGHV) defines two clinically distinct forms of chronic lymphocytic leukemia (CLL) known as mutated (M-CLL) and un-mutated (UM-CLL). To elucidate the molecular mechanisms underlying the adverse clinical outcome associated with UM-CLL, total proteomes from 9 UM-CLL and 9 M-CLL samples were analysed by isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. Unsupervised clustering, based on the expression of 3521 identified proteins, separated CLL samples into two groups corresponding to IGHV mutational status. Computational analysis showed that 43 cell migration/adhesion pathways were significantly enriched by 39 differentially expressed proteins, 35 of which were expressed at significantly lower levels in UM-CLL samples. Furthermore, UM-CLL cells under-expressed proteins associated with cytoskeletal remodelling and over-expressed proteins associated with transcriptional and translational activity. Taken together, our findings indicated that UM-CLL cells are less migratory and more adhesive than M-CLL cells, resulting in their retention in lymph nodes where they are exposed to proliferative stimuli. In keeping with this hypothesis, analysis of an extended cohort of 120 CLL patients revealed a strong and specific association between UM-CLL and lymphadenopathy. Our study illustrates the potential of total proteome analysis to elucidate pathogenetic mechanisms in cancer.
2016-06-27 | PXD001515 | Pride