Ask about this productRelated genes to: BCL11A Blocking Peptide
- 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 Blocking Peptide
Related articles to: BCL11A Blocking Peptide
- The 2025 American Society of Hematology (ASH) Annual Meeting highlighted rapid advances in gene editing for hematologic diseases, with increasing emphasis on precision editing and early exploration of in vivo delivery strategies. Beyond technological development, several measurable parameters are emerging as potential biomarkers, including fetal hemoglobin (HbF), F-cell proportion, HbF/F-cell, editing durability, and long-term clonal monitoring. Clinical studies demonstrated that disruption of the BCL11A enhancer or editing of the HBG1/2 promoter can induce sustained HbF reactivation, which is associated with reduced transfusion burden or transfusion independence in transfusion-dependent β-thalassemia and improved clinical outcomes in sickle cell disease. Near-pancellular HbF distribution and HbF/F-cell levels above anti-sickling thresholds further support the pharmacodynamic value of HbF-related biomarkers. Long-term follow-up studies have also incorporated editing durability and clonal monitoring into safety assessment frameworks. Emerging platforms such as RNA Gene Writer and CD90-targeted virus-like particles have demonstrated the feasibility of in vivo hematopoietic stem cell editing, although challenges related to targeting efficiency, delivery specificity, immunogenicity, and long-term safety remain. Overall, ASH 2025 suggests a shift from achieving gene editing to quantifying efficacy, durability, and safety, with standardized biomarker frameworks likely to play an increasingly important role in future clinical translation. - Source: PubMed
Publication date: 2026/08/05
Zang ZezhouZheng WeiXu RuirongCui Siyuan - In vivo genetic engineering of haematopoietic stem and progenitor cells (HSPCs) holds the potential to revolutionize the treatment landscape for numerous diseases. However, despite its transformative potential, it remains hindered by the difficulty in efficiently and specifically targeting quiescent human HSCs while maintaining their long-term functionality. Here, after screening 15 lipid nanoparticles (LNPs), we report an LNP that efficiently delivers reporter mRNA to human HSPCs both in ex vivo and in vivo settings when conjugated with the anti-CD34 antibody (CD34/LNP). Using CRISPR/Cas editing cargos, CD34/LNP achieves high editing efficiency in human HSPCs ex vivo. Intrafemoral administration of CD34/LNP in humanized mice results in efficient editing of the erythroid-specific BCL11A enhancer within human HSPCs, enabling the sustained long-term reactivation of fetal haemoglobin (HbF) expression in erythroid cells. In a humanized neutropaenia model harbouring an ELANE mutation, intrafemoral administration of CD34/LNP achieves robust editing, targeting exon 2 of ELANE in human HSPCs, partially restoring neutrophil development impairment under long-term observation. Collectively, CD34-targeted delivery enables in vivo HSPC modification without perturbing haematopoiesis, underscoring its suitability for clinical translation. - Source: PubMed
Publication date: 2026/08/05
Du JingjingLuo ZijinXie DanChen YanYang MingLi QiangWang LishaHan LuZhang YimingLi HaiweiLan ZilinShi HaopingLi YinghuiCheng QiangDong FangGao YingdaiYao YaoCheng TaoWei TuoRao Shuquan - Mature plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia (pDC-AML) is a distinct entity with poor prognosis. Yet, the mechanisms underlying the immune evasion and aberrant pDC expansion remain poorly understood. We performed multi-omic profiling of 18 pDC-AML cases, along with 207 non-pDC-AML and 16 BPDCN cases as controls. Single-cell RNA-seq and proteomic analyses demonstrated that pDC-AML leukemia stem cells exhibited unfolded protein response activation, particularly the IRE1α-XBP1 axis, which preceded the acquisition of the pDC maturation program. Supporting this, pharmacological induction of endoplasmic reticulum stress in myeloid cells upregulated BCL11A, the master transcription factor in pDC differentiation, and induced a pDC immunophenotype (CD123BDCA2). Importantly, pDC-AML-derived pDCs exhibited functional impairment, including compromised antigen-presenting pathways and reduced interactions between pDCs and CD8 T cells. scTCR-seq analysis revealed significantly restricted T-cell clonal expansion in the pDC-AML bone marrow microenvironment, which correlated with leukemic burden and reversed upon clinical remission. Notably, allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved overall and progression-free survival, abrogating the prognostic disadvantage relative to non-pDC-AML. Collectively, these findings establish impaired anti-leukemia immunity as a hallmark of pDC-AML, support early HSCT as a clinical priority, and identify ER-stressed pDCs as a potential novel therapeutic target. - Source: PubMed
Publication date: 2026/08/03
Yang XingchengPeng JuanMao XiaZhang LeiHe ShaolongWang ChunyanZhang YichengTang YutingWang JueWei Jia - A zinc finger transcription factor, Bcl11b, is crucial for T-lymphopoiesis. A truncated Bcl11b lacking the C-terminal zinc finger disrupts chromatin accessibility in CD4CD8 double-positive thymocytes. Screening chromatin modifiers associated with this zinc finger identified Cxxc1, a component of the Set1 complex mediating H3K4me3. deficiency arrests the CD4CD8 double-negative-to-double-positive transition, retaining double-negative-like chromatin structure in double-positive thymocytes. Genomic regions bound by Cxxc1 largely overlapped with Bcl11b and were altered upon deficiency. Similar effects are observed in B-lymphocytes via another family protein, Bcl11a, highlighting the role of family proteins in recruiting Cxxc1 in chromatin modulation during lymphopoiesis. - Source: PubMed
Publication date: 2026/08/03
Okuyama KazukiSeo WooseokTakahashi HirotakaMuroi SawakoHou NingIto ShinsukeSawasaki TatsuyaKoseki HaruhikoWu YiboTaniuchi Ichiro - β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. A narrative literature review was conducted using PubMed up to 2025. Search terms included "sickle cell disease," "sickle cell anemia," "β-thalassemia," "transfusion-dependent beta-thalassemia," "gene therapy," "gene addition," "gene editing," "CRISPR-Cas9," "lentiviral vector," "children," "paediatric," and "pediatric." Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly , to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. - Source: PubMed
Publication date: 2026/06/26
Fogliazza FedericaCarbone GiuliaBerzieri MartinaCiriaco DavideEsposito Susanna