MiRNAseq CLL38
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500, Illumina HiSeq 4000
ORGANISM(S): Homo sapiens
SUBMITTER: Dean Bryant
PROVIDER: E-MTAB-12017 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:DNA methylation arrays 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-12018 | biostudies-arrayexpress
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
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: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:Chronic lymphocytic leukemia (CLL) is a highly heterogenous disease, with vastly diverse phenotypes that cause differing clinical courses ranging from benign disease (requiring no treatment), to a rapidly progressive disease and may require aggressive treatment therapy. Key to the B cell is the B-cell receptor (BCR); CLL utilises the BCR to evade apoptosis and promote proliferation and drug resistance through cross-talk between the TME and through BCR activation. Our experiments engage the BCR to determine downstream impact of BCR stimulation on gene expression in CLL (6 hours after stimulation).
2023-05-01 | E-MTAB-12055 | biostudies-arrayexpress
Project description:Series of Chronic Lymphocytic Leukaemia (mix of U-CLL and M-CLL) with and without anti-IgM stimulation of the B cell receptor. RNA acquired at 6hrs and 24hrs post stimulation.
2022-02-21 | E-MTAB-11195 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in western countries, is a clonal accumulation of mature B-lymphocytes and its natural history is yet unclear. By using sequencing and cellular biology approaches on a cohort of CLL patient samples, we show here that acquired CLL mutations are observed in hematopoietic multipotent progenitor fractions in the majority of patients. These early CLL mutations include recurrent inactivating mutations in NFKBIE (10.7%) and missense mutations in BRAF (3.6%) and EGR2 (8.3%). Functional analyses demonstrated that BRAF-G469R affects lymphoid differentiation and transforms the T-cell lineage in vivo. In addition, the EGR2 recurrent mutations were associated with transcriptional activation of EGR2 target genes in patients and cell cycle abnormality in cellular model. Our findings indicate that CLL may develop from an initial infra-clinic, pre-leukemic phase affecting immature hematopoietic cells. We perform RNA-seq experiments on three EGR2-E356K samples, one EGR2-H384N sample and seven EGR2 wildtype patients. The RNA was extracted from B cells. The cDNA libraries were prepared using the ScriptSeq Complete Kit (Epicentre) and we performed paired-end sequencing (100 bp) using HiSeq2000 sequencing instruments.
2015-01-12 | E-MTAB-1776 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status â which distinguishes the two major subtypes of CLL â was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we found widespread heterogeneity in the CLL chromatin landscape, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research. Genome-wide profiling of chromatin states and gene expression levels in 88 CLL samples from 55 individuals gave rise to 88 ATAC-seq profiles, 40 ChIPmentation profiles (10 samples, each with 3 different antibodies and matched immunoglobulin control), and 10 RNA-seq profiles. Raw sequence data has been deposited at the EBI's European Genome-phenome Archive (EGA) under the accession number EGAS00001001821 (controlled access to protect patient privacy).
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