Gene expression profiles in CLL
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22529 | GEO | 2010/06/25
SECONDARY ACCESSION(S): PRJNA128505
REPOSITORIES: GEO
Similar Datasets
Project description:Evaluation of differential expression between CLL patients in a chemoimmunotherapy trial with age-matched controls 41 CLL tumor samples and 11 age matched controls run on both Affy U133A and U133B chips
2010-07-30 | E-GEOD-22529 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is still incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. In order to get more detailed insights into CLL development, we performed a comprehensive proteome analysis of primary human CLL cells and B cells from young and age-matched healthy individuals. For comparison, we also analyzed the chronic B cell leukemia cell line JVM-13 showing rather limited similarity to the primary cells. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and CLL patients. Remarkably, B cells from aged controls displayed significant regulation of proteins related to metabolic processes and stress response in mitochondria such as DLAT, FIS1 and NDUFAB1 as well as DNA repair including RAD9A, MGMT and XPA. Interestingly, these alterations apparently correlating with aging of B cells may also be essential for tumorigenesis and were observed similarly in CLL cells. In CLL cells, in addition, some remarkable unique features like the loss of tumor suppressor molecules PNN and JARID2, and high expression of CCDC88A, PIGR and ID3 otherwise associated with epithelial mesenchymal transition and stemness were determined. Furthermore, while typical hallmarks of cancer such as cell proliferation were hardly apparent for CLL cells, alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify previously unrecognized features of CLL cells and suggest that aging may be accompanied by proteome alterations functionally relevant for predisposing B cells to transform to CLL cells.
2017-12-06 | PXD006589 | Pride
Project description:Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is still incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. In order to get more detailed insights into CLL development, we performed a comprehensive proteome analysis of primary human CLL cells and B cells from young and age-matched healthy individuals. For comparison, we also analyzed the chronic B cell leukemia cell line JVM-13 showing rather limited similarity to the primary cells. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and CLL patients. Remarkably, B cells from aged controls displayed significant regulation of proteins related to metabolic processes and stress response in mitochondria such as DLAT, FIS1 and NDUFAB1 as well as DNA repair including RAD9A, MGMT and XPA. Interestingly, these alterations apparently correlating with aging of B cells may also be essential for tumorigenesis and were observed similarly in CLL cells. In CLL cells, in addition, some remarkable unique features like the loss of tumor suppressor molecules PNN and JARID2, and high expression of CCDC88A, PIGR and ID3 otherwise associated with epithelial mesenchymal transition and stemness were determined. Furthermore, while typical hallmarks of cancer such as cell proliferation were hardly apparent for CLL cells, alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify previously unrecognized features of CLL cells and suggest that aging may be accompanied by proteome alterations functionally relevant for predisposing B cells to transform to CLL cells.
2017-12-06 | PXD006578 | Pride
Project description:Cancer peptide vaccination represents a promising therapeutic approach, but has been hampered by lack of suitable antigens and restricted applicability due to different HLA backgrounds of individual patients. We here introduce a novel warehouse-based concept for composition of personalized peptide vaccines and report on its successful application in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 26 CLL patients in at least partial remission (PR) after 6 months of immuno-chemotherapy were vaccinated with a personalized vaccine compiled from a premanufactured peptide warehouse comprising immunopeptidome-defined CLL-associated peptides. Primary objective was evaluation of immunogenicity, secondary objectives were safety and minimal residual disease (MRD) response. Immunopeptidome-guided vaccine composition was throughout successful, proving the feasibility of warehouse-based vaccine design. Vaccination was well tolerated, with local injection site reactions being the most common adverse event. Only few patients showed vaccine-induced T cell responses, attributable to their inability to mount strong immune responses due to immunechemotherapy and lack of potent adjuvant formulations. Both issues are addressed within a follow-up trial (NCT04688385), combining the immunopeptidome-guided warehouse-based vaccine design reported here with a potent novel adjuvant evaluating personalized multi- peptide vaccination in CLL patients under T cell supportive BTK inhibitor therapies.
2024-11-08 | PXD054248 | Pride
Project description:Evaluation of pretreatment gene expression profiling features in elderly CLL patients; correlation with clinical outcome Evaluation of pretreatment gene expression profiling features in elderly CLL patients enrolled in a clinical trial; correlation with clinical outcome
2012-12-01 | E-GEOD-35935 | biostudies-arrayexpress
Project description:The field of cancer genomics has been empowered by increasingly sophisticated inference tools to distinguish driver mutations from the vastly greater number of passenger mutations. Similarly, promoter DNA hypermethylation has been shown to drive cancer through inactivation of tumor suppressor genes (TSGs), but growing malignant populations also accrue pervasive stochastic epigenetic changes in DNA methylation (DNAme), which likely carry little functional impact. However, the development of DNAme inference methods has lagged behind, providing limited ability to robustly differentiate driver DNAme changes (epidrivers) from stochastic, passenger DNAme changes. To address this challenge, we developed MethSig, a statistical inference framework that accounts for the varying stochastic hypermethylation rates across the genome and between samples. MethSig estimates the background expected DNAme changes, thereby allowing the identification of epigenetically disrupted loci, where observed hypermethylation significantly exceeds expectation, potentially reflecting positive selection. We applied MethSig to reduced representation bisulfite sequencing (RRBS) data of 407 chronic lymphocytic leukemia (CLL) samples, including 304 CLLs collected in a prospective clinical trial. MethSig resulted in well-calibrated quantile-quantile (Q-Q) plots in contrast to ubiquitously used statistical methods, and reproducible inference of epidrivers across independent cohorts. MethSig provided robust inference in additional cancer types, including multiple myeloma (MM, n = 44) and ductal carcinoma in situ (DCIS, n = 24). To further validate MethSig’s inferences, selected CLL candidate epidrivers (DUSP22, RPRM, or SASH1) underwent CRISPR/Cas9 knockout in CLL cells, showing superior fitness in ibrutinib and fludarabine treatment compared with controls. Candidate epidrivers are enriched in known TSGs, and in genes hypermethylated or inactivated across cancer types. Notably, greater number of epidrivers was closely associated with adverse outcome in CLL in a multivariable model accounting for additional adverse prognostic marks. Application of MethSig to CLL relapsed after chemoimmunotherapy further identified relapse-specific epidrivers, enriched in TP53 targets as well as DNA damage pathway. Collectively, MethSig represents a novel framework for robust identification of epidrivers to chart the role of aberrant DNAme in cancer.
2021-05-07 | GSE143673 | GEO
Project description:The miRNA profiles of CLL patients were compared with normal controls.
2020-01-27 | GSE123436 | GEO
Project description:T cells may have a role in sustaining the leukemic clone in chronic lymphocytic leukemia (CLL). In this study, we have examined the ability of T cells from CLL patients to support the survival of the leukemic B cells in vitro. Additionally, we compared global gene expression of T cells from indolent CLL patients with healthy individuals and multiple myeloma (MM) patients. Apoptosis of purified CLL cells was inhibited in vitro when cocultured with increasing numbers of autologous T cells (p<0.01) but not with normal donors. The anti-apoptotic effect exceeded that of the antiapoptotic cytokine IL-4 (p=0.02) and was greater with CD8+ T cells than with CD4+ cells (p<0.05). The effect depended mainly on cell-cell contact although a significant effect was observed in transwell experiments (p<0.05). Additionally, about 356 genes involved in different cellular pathways were deregulated in T cells of CLL patients compared to healthy individuals and MM patients. The results of gene expression profiling was verified for 7 genes (KLF6, TRAF1, CCL4, CCL5, RANTES, XCL1 and XCL2) using qRT-PCR and immunoblotting. Our results demonstrate that CLL-derived T cells can prevent apoptosis of leukemic cells and have altered expression of genes that may facilitate survival of the leukemic clone. Peripheral blood was collected by venipuncture from CLL patients, multiple myeloma (MM) patients and age-matched healthy individuals with informed consent and approval of the local Ethics Committee in keeping with the Helsinki declaration on the use of human subjects for research.
2011-03-23 | E-GEOD-28107 | biostudies-arrayexpress
Project description:Chronic lymphocytic leukaemia (B-CLL) is associated with immune suppression and functional impairment of NK cells, due partly to the reduced expression of activating receptors. We studied the profile of inhibitory checkpoint receptor expression on NK cells from patients with B-CLL. Single, dual and triple expression of the checkpoint receptors PD-1, CTLA-4, LAG-3 and CD96 was increased in patients compared to age-matched healthy controls. PD-1pos cells were present within the late differentiated CD56dim NK pool and showed strong downregulation of all activatory receptors whilst transcriptional profiles revealed a profile of strong receptor signalling. PD-1pos NK cells demonstrated impaired cytokine production and degranulation following target engagement and transfection of PD-1 into NK cell lines directed suppressed cytotoxic function. Importantly, blockade of PD-1:PD-L1 engagement acted to partially reverse these functional defects. These results reveal expression of inhibitory checkpoint receptors to be a new mechanism of NK cell dysfunction in patients with cancer and indicate a potential therapeutic role for single or combinatorial checkpoint blockade to boost immune function in patients with B-CLL.
2024-06-05 | GSE252613 | GEO
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