Ask about this productRelated genes to: BCL11A antibody
- Gene:
- BCL11A NIH gene
- Name:
- BAF chromatin remodeling complex subunit BCL11A
- Previous symbol:
- EVI9
- Synonyms:
- BCL11A-XL, BCL11A-L, BCL11A-S, CTIP1, HBFQTL5, ZNF856
- Chromosome:
- 2p16.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-02-28
- Date modifiied:
- 2019-01-25
Related products to: BCL11A antibody
Related articles to: BCL11A antibody
- Sickle cell disease (SCD) is a monogenic disorder responsible for recurrent vaso-occlusive crises, progressive organ damage, and shortened life expectancy. For decades, allogeneic hematopoietic stem cell transplantation from a matched sibling donor has been the only established cure, but its reach remains limited by donor availability and transplant-related toxicity. The approval of two autologous gene therapy products in 2023, exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel), marked a turning point for the SCD population and the gene therapy field in general. This review proposes a molecular rationale for fetal hemoglobin reactivation and β-globin gene addition, describes the engineering of lentiviral and CRISPR-based platforms, and highlights the clinical evidence accumulated to date that demonstrated durable disease modification with acceptable short-term toxicity. We then assess the clinical positioning of gene therapy within the broader spectrum of curative options compared to current available treatments and address the financial, ethical and psychosocial barriers that limit access to gene therapy both within high-income countries and globally. Critical research priorities include long-term safety surveillance, comparative effectiveness studies, pediatric trials below 12 years, and validated patient-reported outcome instruments. Base editing, non-genotoxic conditioning, and in vivo delivery represent the most promising avenues to broaden access and reduce treatment burden. - Source: PubMed
Publication date: 2026/05/20
Tardif MagalieSaby ManonForté StéphaniePincez Thomas - The genetic architecture of B-cell lymphomas is not fully characterized. We aimed to identify novel candidate variants associated with four common B-cell lymphoma subtypes-diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (MZL)-through cross-trait analyses with correlated idiopathic inflammatory myopathies subtypes, dermatomyositis (DM) and polymyositis (PM). Leveraging shared genetic susceptibility with DM and PM, we applied a pleiotropy-informed conditional false discovery rate (condFDR) method to recompute nominal single nucleotide polymorphism association -values for each B-cell lymphoma subtype. Associations were considered significant at condFDR <0.01. Functional annotation was performed using FUMA (Functional Mapping and Annotation of Genome-Wide Association Studies), followed by Gene Ontology (GO) enrichment analysis via clusterProfiler, with similar GO terms clustered for interpretation and visualization. We identified 4, 2, 13, and 6 novel candidate loci for DLBCL, FL, CLL, and MZL, respectively. Most loci exhibited regulatory effects on genes involved in adaptive immune responses and cell death pathways. Notably, for DLBCL locus 1q23.3 affects SLAMF genes implicated in natural killer and lymphocyte activation. A trans-eQTL at 2q13 for FL was associated with BCL11A, a multifunctional oncogene. For CLL, a novel locus at 16q24.1 regulates IRF8, a known CLL risk gene. Functional mapping of previously reported CLL risk loci revealed RIPK1 (6p25.2), linked to necroptosis. No enriched biological pathways were detected for MZL risk-associated genes. These findings advance our understanding of the genetic architecture of four B-cell lymphoma subtypes and aim to inform future genetic and functional studies. - Source: PubMed
Publication date: 2026/05/09
Che Weng IanJarvis James NInternational Lymphoma Epidemiology Consortium InterLymph Imacs Genetics Group Myogen Lundberg Ingrid ESmedby Karin ELamb Janine AHolmqvist Marie - This chapter presents a comprehensive quantitative framework for identifying and evaluating therapeutic targets for -globin gene disorders through detailed modeling of the fetal-to-adult hemoglobin switch. The biological foundations of -thalassemia and related hemoglobinopathies are reviewed, with particular emphasis on the regulatory network governing - to -globin gene expression. A hybrid Petri net methodology is applied to capture the dynamics of transcriptional regulators, chromatin-remodeling complexes, and globin gene interactions. Both targeted drug-based and RNAi-mediated gene-therapy strategies are examined through computer simulations. Model calibration and validation are performed using available qPCR and RT-qPCR data for key regulators, enabling reliable estimation of kinetic parameters and prediction of treatment outcomes. Comparative analyses of existing interventions identify MS-275 and ACY-957 as the most effective drug-based inducers of -globin, while CHD4-targeting RNAi emerges as the most potent among established gene therapies. The modeling framework further predicts two novel therapeutic strategies: inhibition of the erythroid transcription factor complex as a drug target, and combined silencing of BCL11A, FOG1, and HDAC1/2 as RNAi-mediated gene-therapy approach. Both strategies produce significantly greater -globin induction than currently known treatments. Overall, the chapter demonstrates how hybrid PNs can serve as a powerful computational tool for mechanistically guided target discovery in -globin disorders and related genetic diseases. - Source: PubMed
Bashirov Rza - Studies have shown that substance use liability is associated with novelty seeking, anxiety-like behavior, and pain sensitivity. We examined whether common genetic variation in outbred Sprague-Dawley rats explained variation in behavioral measures from three assays with established links to substance use: locomotor response to a novel environment, elevated plus maze, and tail flick. We estimated single-nucleotide polymorphism heritability and performed genome-wide association analyses using permutation-derived significance thresholds (N = 534-654 rats across traits). Heritability estimates ranged from 0.14 to 0.38 across 11 traits. Three independent loci were identified: chromosome 1 for elevated plus maze open-arm behavior (α = 0.05), chromosome 14 for elevated plus maze immobility (α = 0.10), and chromosome 17 for tail flick latency (α = 0.05). Candidate genes included Slc18a2, Gfra1, and Pdzd8 (chromosome 1); Rel and Bcl11a (chromosome 14); and Eci2 and Eci3 (chromosome 17). We compared these loci with our genome-wide association study of a F intercross of selectively bred high- and low-responder rats, originally derived from Sprague-Dawleys, that model individual differences in externalizing and internalizing behavior. The current loci are distinct from the ones identified in the bred lines. This difference likely reflects selection history in the high- and low-responder Fs, which focused on facets of exploratory locomotion, while loci for anxiety and pain sensitivity traits were identified in the outbreds. This highlights the benefit of using both outbred and selectively bred rats to probe causal variants contributing to individual differences in substance use liability. The current outbred findings implicate monoaminergic signaling, transcriptional control, and lipid metabolism as testable mechanisms for addiction-relevant behaviors. - Source: PubMed
Chitre Apurva SHebda-Bauer Elaine KEmery Michael ALi FeiNguyen Khai-MinhWang YizhiCheng RiyanPolesskaya OksanaWatson Stanley JLi JunAkil HudaPalmer Abraham A - Reactivating fetal hemoglobin (HbF) has become a key therapeutic strategy for β-hemoglobinopathies. However, the regulatory networks controlling HbF are complex and have only recently been uncovered. This review integrates current knowledge of the genetic and epigenetic factors that influence HbF expression, including BCL11A, HBS1L-MYB, KLF1, and variants associated with HPFH, and shows how these pathways work together to regulate γ-globin levels. It also highlights recent advances in HbF-targeted treatments, including gene-editing technologies such as CRISPR-Cas9-based BCL11A enhancer disruption, promoter editing to mimic hereditary persistence of fetal hemoglobin (HPFH), and advanced tools like base and prime editing. By combining mechanistic understanding with therapeutic development, this review highlights how improvements in HbF regulation have transformed efforts to find cures for sickle cell disease and β-thalassemia, while also revealing new opportunities for targeted HbF induction across different patient groups. - Source: PubMed
Publication date: 2026/05/01
Abu Za'ror Yousef Saeed MohammadSuleiman Joseph BagiDelmani Fatima AzzahraAlhmoud Jehad FAyasreh Amer MohammadAl-Wendawi Sarah IhsanAlRamadneh Tareq NayefAzlan Maryam