Ask about this productRelated genes to: Bcl3 antibody
- Gene:
- BCL3 NIH gene
- Name:
- BCL3 transcription coactivator
- Previous symbol:
- D19S37, BCL4
- Synonyms:
- -
- Chromosome:
- 19q13.32
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2019-01-25
Related products to: Bcl3 antibody
Related articles to: Bcl3 antibody
- Prostate cancer (PC) progression is increasingly recognized as a dynamic, inflammation-driven process in which chronic immune dysregulation contributes to disease aggressiveness and therapeutic resistance. Among inflammatory signaling pathways, nuclear factor kappa B (NF-κB) has been consistently implicated in prostate tumorigenesis, castration resistance, and apoptosis resistance. However, despite the extensive literature on NF-κB biology, the mechanisms by which its dysregulation is sustained and functionally shaped during PC progression remain incompletely understood. This review synthesizes current evidence on prostate cancer-specific NF-κB signaling, with an emphasis on stage-dependent activation, molecular regulation within the tumor microenvironment, and downstream transcriptional programs linked to survival and treatment resistance. Particular attention is given to the regulatory role of B-cell lymphoma-3 (BCL-3), an atypical nuclear IκB protein, and its potential interplay with B-cell lymphoma-2 (BCL-2), a well-established NF-κB-regulated anti-apoptotic factor in PC. Available clinical, molecular, and transcriptomic data support constitutive NF-κB activation across multiple stages of PC, particularly in advanced and castration-resistant disease. Although BCL-2 overexpression is well documented as a mediator of apoptosis resistance in PC, evidence directly linking BCL-3 to BCL-2 regulation in this disease remains limited. Data from other malignancies suggest that BCL-3 can modulate NF-κB transcriptional output and enhance BCL-2 expression; however, prostate-specific mechanistic validation is lacking. We propose a testable, hypothesis-driven model in which BCL-3 may function as a context-dependent regulator of NF-κB-mediated survival signaling in PC, potentially influencing BCL-2 expression and therapeutic resistance. However, this relationship remains speculative and is not yet supported by direct mechanistic evidence in PC. By distinguishing between established evidence and inferred mechanisms, this review highlights critical knowledge gaps and outlines experimental strategies to clarify the functional relevance of the BCL-3/BCL-2 axis. Improved understanding of NF-κB regulatory dynamics may inform the development of more precise, stage-adapted therapeutic strategies for advanced PC. - Source: PubMed
Publication date: 2026/04/13
Al-Hakm RanyahAltaie Alaa MuayadBoghossian AnaniaBendardaf RiyadTalaat Iman MHamoudi Rifat - Approximately 1% of chronic lymphocytic leukemia (CLL) cases harbor a translocation juxtaposing the () and () loci. Aiming at comprehensive molecular characterization of ::positive B-cell neoplasms, we here investigated samples from 84 patients using fluorescence in situ hybridization (FISH), whole-genome and targeted sequencing, and DNA methylation analyses. Junctional sequences obtained in 27 patients showed breakpoints upstream of in all CLL cases. breaks were presumably driven by aberrant class-switch recombination in 26/27 cases, frequently involving (12/26). Notably, 95% (78/82) of patients carried an unmutated with significant CLL stereotype subset #8 enrichment. Trisomy 12 (61%, 51/83) and mutations affecting (32%, 25/79), (14%, 11/79), and (14%, 11/79) were frequent aberrations. DNA methylation analysis assigned 77% (51/66) of patients with ::translocation with at least 60% tumor cell content to the naive B-cell-like group but unraveled a distinct and during follow-up stable signature resembling in part plasma cell-like epigenetic features. A binary DNA methylation classifier using 20 CpGs could distinguish ::-translocated CLL samples from other CLL subtypes. In an efficacy cohort of 3832 previously untreated patients from GCLLSG trials, was associated with shorter progression-free survival (PFS) and overall survival (OS) in 28 patients when treated with chemoimmunotherapy, but not in those receiving venetoclax. Our findings highlight the genetic and epigenetic homogeneity of ::-translocated CLL samples and their differences from other types of CLL, suggesting :: leukemic B-cell neoplasms to be a biological distinct type within the spectrum of mature lymphatic leukemia/CLL. - Source: PubMed
Publication date: 2026/04/29
Drewes CosimaLópez CristinaMartinez-Manjón Juan EmilioOkeke NnamdiJebaraj BillyBens SusanneBrändl BjörnDyer Martin J SEichhorst BarbaraFischer AnjaFischer KirstenRobrecht SandraHallek MichaelGlaser SelinaHillebrecht SinaJayne SandrineKretzmer HeleneMottok AnjaMüller Franz-JosefSchneider ChristofAmmerpohl OleDel Val CoralStilgenbauer StephanTausch EugenSiebert Reiner - Activation of oncogenes by hijacking immunoglobulin gene loci (IG) enhancers via chromosomal translocation is a common pathogenetic mechanism in B-cell malignancies, affecting 5-10% of chronic lymphocytic leukemia (CLL). The oncogenic partners in many of these cases remain unidentified. Therefore, we conducted a comprehensive analysis of 144 CLL samples with IGH-translocation excluding IGH::BCL2, IGH::CCND1, IGH::BCL3 and IGH::MYC. By combining fluorescence in situ hybridization (FISH) with whole-genome, targeted sequencing, and RNA expression profiling, we identified 25 IG-translocation partners; 12 were previously unreported. Of 142 cases, 107 (75%) displayed an unmutated IGHV. Genetic profiling showed a heterogenous distribution of chromosomal aberrations and recurrently mutated genes across the groups. Of 41 informative cases, 32 (78%) exhibited breakpoints driven by aberrant class-switch recombination (CSR), with prominent involvement of IGHM (9/41) and IGHG3 (9/41). Three cases with unmutated IGHV carried a juxtaposition of the IGH locus 5' to the intact NKX2.6 gene in chromosome 8p21.2 due to illegitimate VDJ recombination, associated with significant ectopic upregulation of NKX2.6 transcriptional expression (FDR < 0.001, logFC: 15). Similarly, METRNL, located at the telomere of chromosome 17q25, was identified as a translocation partner gene in four cases. Our findings expand the spectrum of the oncogenic translocation partners targeting IGH in CLL. - Source: PubMed
Publication date: 2026/04/23
Drewes CosimaLópez CristinaOkeke NnamdiJebaraj BillyWiegreffe ChristophKraus IsabelleHillebrecht SinaAwada AmaniBens SusanneChteinberg EmilEichhorst BarbaraDatismann SarahDyer Martin J SFischer AnjaFischer KirstenGlaser SelinaHallek MichaelKretzmer HeleneMottok AnjaPfaff DominickSchnitzler KarolineMeier-Kolthoff Jan PSchlesner MatthiasSchneider ChristofBritsch StefanAmmerpohl OleStilgenbauer StephanTausch EugenSiebert Reiner - The inflammation-intestinal metaplasia (IM)-carcinoma cascade has been proposed as a framework for gastric cancer (GC) development, yet the cell-level heterogeneity and microenvironmental remodeling underlying this progression remain poorly characterized. Here, we constructed a single-cell transcriptomic atlas by integrating scRNA-seq data from chronic gastritis (superficial, CGS), IM, cancer-adjacent, and tumor tissues through a unified analytical pipeline. Seven major cell lineages were resolved. Relative to CGS, IM and GC tissues exhibited a progressive contraction of epithelial compartments accompanied by expansion of immune and stromal populations. Copy number variation (CNV) inference identified two tumor-restricted malignant epithelial subgroups-one biased toward differentiation and the other enriched for inflammatory and epithelial-mesenchymal transition (EMT) signatures-as well as putative proto-malignant intermediates that coexisted with phenotypically normal epithelium. Cell-cell communication analysis indicated broadly augmented crosstalk between epithelial cells and T cells, myeloid cells, and fibroblasts, with prominent involvement of a CD44-extracellular matrix (ECM) axis. Pseudotime trajectory analysis placed malignant epithelium at late positions along gastric and pyloric mucosal cell differentiation backbones, coinciding with increasing CNV burden and enrichment of stem-like transcriptional programs. Gene regulatory network analysis revealed coordinated activity of lineage-specification modules (HNF4/CDX, NR1H4/ESRRA), proliferative regulons (MYC/TFDP1), and inflammatory/EMT-associated programs (FOSL1/REL/NF-κB). In independent cohorts, elevated expression of several malignant-epithelium-associated transcription factors-including HNF4A, KLF3, FOSL1, TCF7L2, BCL3, RELB, ONECUT2, and MAF-correlated with unfavorable overall survival. Collectively, these findings provide single-cell-resolution evidence consistent with the proposed three-stage model of gastric carcinogenesis and highlight candidate transcriptional regulators warranting further investigation as potential early-detection biomarkers. - Source: PubMed
Publication date: 2026/04/22
Li XiulanGuo MengqiWen YunhanLong Bo - Long-term exposure to the chemical industry pollutant benzene induces hematopoietic damage; however, the mechanism of this injury is unclear. Using an integrative RNA-seq analysis of benzene-exposed samples, we identified Y-box binding protein 1 (YBX1) and neurogenic locus notch homolog protein 1 (NOTCH1) as the most significantly dysregulated apoptosis-related molecules, prompting us to investigate their functional interplay. While neurogenic locus notch homolog protein 1 (NOTCH1) drives the progression of both benign and malignant disorders, the involvement of Y-box binding protein 1 (YBX1) despite being extensively characterized in tumorigenesis remains unexplored in the context of benzene-induced hematopoietic injury. This study examines the molecular mechanism of the YBX1/NOTCH1 axis in benzene-mediated monocyte apoptosis. Accordingly, we combined clinical data with RNA seqenceing (RNA-seq) analysis and examined the mechanistic basis of benzene-induced apoptosis in human monocytic leukemia cells using Cell Counting Kit-8 (CCK-8) cell viability assays, flow cytometry (FC), DNA pull-down coupled with liquid chromatography-tandem mass spectrometry (LC-MS), and western blotting (WB). Analysis of 1,4-BQ-treated THP-1 cells revealed that 1,4-Benzoquinone (1,4-BQ) upregulated NOTCH1/transcription coactivator BCL3 (BCL3) and downregulated YBX1/apoptosis regulator Bcl-2 (BCL2) in their gene profiles and protein levels. Furthermore, the differentially expressed genes were enriched in apoptotic pathways. Treatment with 1,4-BQ inhibited THP-1 cell proliferation, induced S-phase arrest, and triggered apoptosis in a concentration- and time-dependent manner. Knockdown of NOTCH1 or overexpression YBX1 significantly eliminated the inhibitory effects of 1,4-BQ on upregulated BCL3 and downregulated BCL2 expression. Furthermore, the inhibitory effects on apoptosis were considerably offset by YBX1 overexpression or NOTCH1 knockdown. YBX1 regulates BCL2/BCL3 by inhibiting NOTCH1, mediating benzene-induced monocyte apoptosis. Taken together, our results uncovered a critical role of YBX1/NOTCH1 in the benzene-induced monocyte apoptosis, which may have great potential as a biomarker and therapeutic target in benzene-induced hematotoxicity. - Source: PubMed
Chen Qi JunWu Li MeiZeng Wen FengYang Zhi QianKuang LuLiu Zeng HuiLiu Da BinLiu Xue HuiLiao Hai XiuLiu Shu YanWu Shao Guo