Oncogenic role of the DNMT1 in diffuse large B-cell lymphomas [BSRR]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1230146 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR32537348_1.fastq.gz | Fastqsanger.gz | |||
| SRR32537348_2.fastq.gz | Fastqsanger.gz | |||
| SRR32537349_1.fastq.gz | Fastqsanger.gz | |||
| SRR32537349_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
Similar Datasets
Project description:Oncogenic role of the DNMT1 in diffuse large B-cell lymphomas [RNA-seq]
| PRJNA1230147 | ENA
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, demonstrates significant molecular heterogeneity and suboptimal clinical outcomes. Notably, 10%-15% of patients develop primary refractory disease following first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen. While epigenetic modulators have emerged as potential therapeutic options for these high-risk cases, clinical application of broad-spectrum DNA methyltransferase inhibitors such as decitabine and azacitidine remains limited by their multi-target toxicity profiles. In this study, we demonstrated that DNA methyltransferase 1 (DNMT1) plays a critical oncogenic role in DLBCL pathogenesis.
2025-04-13 | GSE290802 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, demonstrates significant molecular heterogeneity and suboptimal clinical outcomes. Notably, 10%-15% of patients develop primary refractory disease following first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen. While epigenetic modulators have emerged as potential therapeutic options for these high-risk cases, clinical application of broad-spectrum DNA methyltransferase inhibitors such as decitabine and azacitidine remains limited by their multi-target toxicity profiles. In this study, we demonstrated that DNA methyltransferase 1 (DNMT1) plays a critical oncogenic role in DLBCL pathogenesis.
2025-04-13 | GSE290803 | GEO
Project description:Genomic Variation in Diffuse Large B Cell Lymphomas
| PRJNA400524 | ENA
Project description:Constitutive activation of the anti-apoptotic NF-κB signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL) that is characterized by adverse survival. Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 mutants in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of β-Catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3β to oncogenic CARMA1. Recruitment of the β-Catenin destruction complex was independent of CARMA1-BCL10-MALT1 (CBM) complex formation or constitutive NF-κB activation and promoted the stabilization of β-Catenin. Elevated β-Catenin expression was detected in cell lines and biopsies from ABC DLBCL that rely on chronic BCR signaling. Increased β-Catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, β-Catenin enhanced expression of immune suppressive IL-10 and repressed anti-tumoral CCL3, indicating that β-Catenin may induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and β-Catenin signaling by gain-of-function mutations in CARMA1 can augment WNT stimulation and is required for maintaining high expression of distinct NF-κB target genes and can thereby trigger cell intrinsic and extrinsic processes that promote DLBCL lymphomagenesis. CARMA1 mutants were expressed in BJAB, an NF-κB negative GCB DLBCL lymphoma cell line. Gene expression induced by GCB DLBCL derived CARMA1 L225LI mutant was compared with the empty vector (mock) control, CARMA1 WT, CARMA1 point mutant R35A and with CARMA1 double mutant R35A/L225LI.
2016-07-03 | E-GEOD-70025 | biostudies-arrayexpress
Project description:Intrinsic resistance of lymphoma cells to apoptosis is a probable mechanism causing chemotherapy resistance and eventual fatal outcome in patients with diffuse large B cell lymphomas (DLBCL). We investigated whether microarray expression profiling of apoptosis related genes predicts clinical outcome in 46 patients with primary nodal DLBCL. Unsupervised cluster analysis using genes involved in apoptosis (N=246) resulted in 3 separate DLBCL groups partly overlapping with GCB versus ABC like phenotype. One group with poor clinical outcome was characterized by high expression levels of pro-and anti-apoptotic genes involved in the intrinsic apoptosis pathway. A 2nd group, also with poor clinical outcome, was characterized by high levels of apoptosis inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. The 3rd group showing a favourable outcome was characterized by low expression levels of genes characteristic for both other groups. Our results suggest that chemotherapy refractory DLBCL are characterized either by an intense cellular cytotoxic immune response or by constitutive activation of the intrinsic mediated apoptosis pathway with concomitant downstream inhibition of this apoptosis pathway. Consequently, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective as alternative treatment modality in part of chemotherapy refractory DLBCL. Keywords: expression profiling B lymphomas
2006-12-08 | GSE3892 | GEO
Project description:Constitutive activation of the anti-apoptotic NF-κB signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL) that is characterized by adverse survival. Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 mutants in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of β-Catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3β to oncogenic CARMA1. Recruitment of the β-Catenin destruction complex was independent of CARMA1-BCL10-MALT1 (CBM) complex formation or constitutive NF-κB activation and promoted the stabilization of β-Catenin. Elevated β-Catenin expression was detected in cell lines and biopsies from ABC DLBCL that rely on chronic BCR signaling. Increased β-Catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, β-Catenin enhanced expression of immune suppressive IL-10 and repressed anti-tumoral CCL3, indicating that β-Catenin may induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and β-Catenin signaling by gain-of-function mutations in CARMA1 can augment WNT stimulation and is required for maintaining high expression of distinct NF-κB target genes and can thereby trigger cell intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.
2016-01-01 | GSE70025 | GEO
Project description:Oncogenic role of SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2 positive diffuse large B-cell lymphomas
| PRJNA745982 | ENA
Project description:Deep characterization of a large series of splenic diffuse red pulp lymphomas
2017-12-23 | GSE65060 | GEO
Project description:Oncogenic role of SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2 positive diffuse large B-cell lymphomas [RNA-seq]
| PRJNA746334 | ENA