Multimodal single-cell profiling identifies distinct patterns of T-cell infiltration in nodal B-cell lymphoma entities
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252608 | GEO | 2024/01/28
REPOSITORIES: GEO
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Project description:The redirection of T-cells has emerged as an attractive therapeutic principle in B-cell non-Hodgkin lymphoma (B-NHL). However, a detailed characterization of lymphoma-infiltrating T-cells across B-NHL entities is missing. Here, we present single-cell transcriptome and T-cell receptor sequencing of lymph-node derived T-cells from patients with diffuse large B-cell, mantle cell, follicular, or marginal zone lymphoma, and from healthy controls. These data revealed quantitative aberrations of the T-cell microenvironment across and within B-NHL entities.
2024-01-28 | GSE252455 | GEO
Project description:The two B-cell non-Hodgkin lymphoma (NHL) entities chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) show recurrent chromosomal gains of 3q25 q29, 12q13 q14 and 18q21-q22. The pathomechanisms affected by these aberrations are not understood. The aim of this study was to identify genes, located within these gained regions, which control cell death and cell survival of MCL and CLL cancer cells. Blood samples from 24 CLL and 6 MCL patients as well as 6 cell lines representing both malignancies were analyzed by gene expression profiling. By comparison of genomic DNA and gene expression, 72 candidate genes were identified. We performed a limited RNAi screen with these candidates in order to identify genes affecting cell survival. CCDC50, SERPINI2 and SMARCC2 mediated a reduction of cell viability in primary CLL cells as well as in cell lines. Gene knock down and a NFkB reporter gene assay revealed that CCDC50 is required for survival in MCL and CLL cells and controls NFkB signaling. This SuperSeries is composed of the SubSeries listed below.
2010-06-03 | GSE16413 | GEO
Project description:Synchronous tumors are a rare disease and the underlying mechanism is seldom discussed. Here we present a case study of synchronous primary neoplasms detected in three distinct tissues: mantle cell lymphoma (MCL), clear cell renal cell carcinoma (ccRCC) and gastrointestinal stromal tumor (GIST). MCL is one form of B-cell non-Hodgkin’s lymphoma (NHL) that affects approximately 6% of NHL patients. GIST is thought to be derived from the Interstitial Cells of Cajal, a group of mesenchymal cells in the gastrointestinal tract involved in peristaltic motor activity. ccRCC tumor cells are the most common malignancy of kidney cancer and are characterized by enlarged cytoplasms. Genomic DNA from FFPE tumor sections and control DNA extracted from saliva were heat-fragmentated, labeled, hybridized and scanned following manufacturer’s recommendation for 244K arrays (Agilent). Raw data were background corrected and normalized in R. Nexus v4.1 (Biodiscovery) software was then used to call aberrant regions using Rank Segmentation algorithm from the processed data. Genes within aberrant regions can be indicated as copy number gain or loss accordingly. To identify significantly enriched canonical pathways, upstream and downstream genes for several cancer-related pathways were explored in Ingenuity knowledge base (Ingenuity Systems) and Genespring GX-10 (Agilent) with their copy number change status checked in Nexus. The analysis revealed high copy-number amplifications in gene regions related to an anti-apoptotic and cell-growth promoting pathway in all three cancers. Genomic DNA was isolated from mantle cell lymphoma (MCL), clear cell renal cell carcinoma (ccRCC) and gastrointestinal stromal tumor (GIST) FFPE tumor sections using the WaxFreeTM DNA Extraction Kit (TrimGen). Control DNA extracted from saliva was collected using a saliva self-collecting kit (Oragene). Heat-fragmentation, one-cycle target labeling, hybridization and scanning of the DNA were performed following manufacturer’s recommendation for 244K arrays (Agilent). The arrays were scanned by using the Agilent Scanner G2505B and Agilent Feature Extraction software v10.5 to produce raw data files. Raw data were background corrected and normalized in R. Nexus v4.1 (Biodiscovery) software was then used to call aberrant regions using Rank Segmentation algorithm from the processed data. Genes within aberrant regions can be indicated as copy number gain or loss accordingly.
2010-08-02 | E-GEOD-22905 | biostudies-arrayexpress
Project description:B cell non-Hodgkin's lymphoma (B-NHL) consists of different pathological entities that are frequently characterized by distinct genetic alterations. However, the knowledge on these genetic lesions in B-NHL is still limited. In order to obtain a more comprehensive view of genetic lesions in B-NHL, we performed genome-wide analysis of copy number (CN) alterations as well as allelic imbalances using Affymetrix SNP arrays with B-NHL cases, including SNP array data were analyzed with CNAG/AsCNAR software, which enabled sensitive detection of CN alterations in allele-specific manner, and thus allelic imbalances, without depending on availability of paired normal controls. Most frequent numerical abnormalities in B-NHL were gains of chromosomes 3 and 18, although gains of chromosome 3 were less prominent in FL. Chromosomal deletions that lead to loss of heterozygosity (LOH) were commonly found in 1p, 6q and 10q. High-grade amplifications and homozygous deletions frequently provide a clue to identify relevant gene targets. In our series, 12 loci of high-grade amplifications and 14 loci of homozygous deletions were identified, and helped to specify the candidate genes. These regions included, FCGR2B amplified in 5 cases of DLBCL, RERE amplified in 2 cases of FL and CDKN2A/CDKN2B deleted in 9 cases of DLBCL. To identify oncogenic lesions in neuroblastoma, we performed a genome-wide analysis of primary tumor samples from 241 lymphoma samples (238 fresh tumors and 3 cell lines) using high-density 50K and/or 250K SNP arrays (Affymetrix GeneChip).
2009-05-01 | E-GEOD-12906 | biostudies-arrayexpress
Project description:The spectrum of entities, the therapeutic strategy and the outcome of mature aggressive B-cell lymphomas (maB-NHL) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHL have been studied in detail, data on molecular profiling of pediatric maB-NHL are hitherto lacking. Our aim was to characterize pediatric maB-NHL on the molecular level and to evaluate whether a molecular diagnosis of pediatric maB-NHL reveals clinically relevant groups. Keywords: pediatric disease state analysis
2008-06-17 | GSE10172 | GEO
Project description:Non-Hodgkin lymphomas (NHL) make up the majority of lymphoma diagnoses and represent a very diverse set of malignancies. We sought to identify kinases uniquely upregulated in different NHL subtypes. Using Multiplexed Inhibitor Bead-mass spectrometry (MIB/MS), we found Tyro3 was uniquely upregulated and important for cell survival in primary effusion lymphoma (PEL), which is a viral lymphoma infected with Kaposi’s sarcoma-associated herpesvirus (KSHV).
2019-07-11 | PXD012087 | Pride
Project description:Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin’s lymphoma (NHL). In cancers, tumour suppressive microRNAs may be silenced by DNA hypermethylation. By microRNA profiling, miR-155-3p was significantly upregulated upon demethylation treatment of MCL cell lines with 5-aza-2’-deoxycytidine (5-azadC). Methylation-specific PCR, verified by pyrosequencing, showed complete methylation of miR-155-3p in one MCL cell line (REC-1). 5-azadC treatment of REC-1 led to demethylation and re-expression of miR-155-3p. Over-expression of miR-155-3p led to increased sub-G1 apoptotic cells and reduced cellular viability, demonstrating its tumour suppressive properties. By luciferase assay, lymphotoxin-beta (LT-β) was validated as a miR-155-3p target. In 31 primary MCL, miR-155-3p was found hypermethylated in 6(19%) cases. To test if methylation of miR-155-3p was MCL-specific, miR-155-3p methylation was tested in an additional 191 B-cell, T-cell and NK-cell NHLs, yielding miR-155-3p methylation in 66(34.6%) including 36(27%) non-MCL B-cell, 24(53%) T-cell and 6(46%) of NK-cell lymphoma. Moreover, in 72 primary NHL samples with RNA, miR-155-3p methylation correlated with miR-155-3p downregulation (p=0.030), and LT-β upregulation (p=0.004). Collectively, miR-155-3p is tumour suppressive microRNA hypermethylated in MCL and other NHL subtypes. As miR-155-3p targets LT-β, which is an upstream activator of the non-canonical NF-kB signalling, miR-155-3p methylation is potentially important in lymphomagenesis
2014-08-31 | GSE57128 | GEO
Project description:Covalent Bruton's tyrosine kinase inhibitors (BTKis) have transformed the treatment of B-cell non-Hodgkin lymphoma (B-NHL), including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), but their activity has been limited by off-target toxicity and acquired drug resistance. TG-1701 is a novel irreversible and highly specific BTKi being presently under study in a phase 1 clinical trial in patients with relapsed/refractory B-NHL alone and in combination with ublituximab, a CD20 antibody, and umbralisib, a dual PI3Kδ and CK1ε inhibitor. Here we show, for the first time that phosphoproteomic analysis of CLL patients receiving a BTKi (TG-1701) led to a non-supervised clustering that matched the clinical outcomes and separated a group of “responders” from a group of “non-responders”. This clustering was based on a selected list of 96 phosphosites, with Ikaros-Ser442/445 phosphorylation as a potential marker for TG-1701 efficacy. RNA-seq analysis followed by qPCR and western blot validation further revealed that TG-1701 treatment blunted the Ikaros gene signature only in responder patients, as well as in BTKi-sensitive, but not BTKi-insensitive, B-NHL cell lines and xenografts. Importantly, and in contrast with ibrutinib, TG-1701 did not impair FcγR-driven antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) triggered by the anti-CD20 antibodies rituximab and ublituximab in a multicellular MCL co-culture system. In addition, TG-1701 cooperated with ublituximab coupled to umbralisib (also referred as the U2 regimen) in reducing the tumor growth in both ibrutinib-sensitive and ibrutinib-insensitive mouse models of MCL. Altogether, these data validate phosphoproteomic as a broken thread to omics analysis in the clinic and support the use of TG-1701-U2 combination in R/R B-NHL patients, irrespective of prior response to ibrutinib.
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Project description:The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma Keywords: lymphochip; MCL; untreated Tumor biopsies from 71 untreated patients with mantle cell lymphoma
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