BCL11B (B-cell lymphoma/leukaemia 11B)
2004-07-01 Roderick A F MacLeod , Stefan Nagel AffiliationDSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen, Mascheroder Weg 1b 38124, Braunschweig, Germany
Identity
HGNC
LOCATION
14q32.2
IMAGE
LOCUSID
ALIAS
ATL1,ATL1-alpha,ATL1-beta,ATL1-delta,ATL1-gamma,CTIP-2,CTIP2,IDDFSTA,IMD49,RIT1,ZNF856B,hRIT1-alpha
FUSION GENES
DNA/RNA
Description
ORF comprises 4 exons, exon 3 being alternately spliced, while the 3 part of exon 4 is untranslated. Alternative splice variants due to presence (var.1) or absence (var.2) of exon 3.
Transcription
In a telomeric --> centromeric orientation.
Proteins
Description
894 amino acids, 95.5 kDa; contains 6 krueppel-like Zn-finger domains and a proline-rich region
Expression
Normal expression in thymus and brain; malignant expression in T-cell neoplasia and Ewing-family tumors.
Localisation
Inner nuclear membrane; colocalization with heterochromatin protein (HP1) and histone deacetylase SIRT1 suggests role as transcriptional repressor.
Function
Poorly defined; transcriptional repressor; developmentally regulates thymic differentiation and survival; inhibits HIV-1 Tat transactivation and repression of viral replication.
Homology
BCL11A on chromosome 2p13.
Mutations
Somatic
Unrecorded in humans. Biallelic mutation/deletion in mouse thymic lymphomas induced by ionizing radiation.
Implicated in
Entity name
Disease
First detected as translocation partner of TLX3 (alias HOX11L2) in 15-20% pediatric cortical T-ALL with possible male bias; subsequently confirmed in adult T-ALL, albeit less frequently.
Prognosis
May be poor via strong cytogenetic assocation with TLX3 which reportedly confers adverse prognosis.
Cytogenetics
Additional known recurrent rearrangements reportedly absent from t(5;14) patients.
Oncogenesis
Distal regulatory elements drive ectopic expression of TLX3 in T-ALL and possibly other related NK-family Hox genes, viz. NKX2-5. Tumor suppressor role reported in mouse yet to be confirmed in man.
Breakpoints
Note
t(5;14) breakpoints are widely scattered over 1.2 Mbp downstream of BCL11B probably targeting distal enhancer(s) posited to lie in the "gene desert" separating BCL11b from VRK1. This region has been recently shown to carry multiple Dnase-I sensitive sites in T-cells which may represent a locus control region. The solitary AML breakpoint lies upstream of BCL11B and its significance has yet to be established.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 12196208 | 2002 | COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein. | Avram D et al |
| 11587205 | 2001 | A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. | Bernard OA et al |
| 15104287 | 2004 | A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene. | Bezrookove V et al |
| 14504110 | 2004 | Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951. | Cavé H et al |
| 14732688 | 2004 | Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites. | Crawford GE et al |
| 15325104 | 2004 | BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia. | MacLeod RA et al |
| 14500364 | 2003 | The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2). | Nagel S et al |
| 12692243 | 2003 | Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. | Rohr O et al |
| 14754877 | 2004 | Involvement of V(D)J recombinase in the generation of intragenic deletions in the Rit1/Bcl11b tumor suppressor gene in gamma-ray-induced thymic lymphomas and in normal thymus of the mouse. | Sakata J et al |
| 11719382 | 2001 | The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. | Satterwhite E et al |
| 12930829 | 2003 | Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression. | Senawong T et al |
| 14697215 | 2004 | Two distinct methods analyzing chromatin structure using centrifugation and antibodies to modified histone H3: both provide similar chromatin states of the Rit1/Bcl11b gene. | Togashi T et al |
| 12717433 | 2003 | Bcl11b is required for differentiation and survival of alphabeta T lymphocytes. | Wakabayashi Y et al |
| 15194534 | 2004 | Two dual-color split signal fluorescence in situ hybridization assays to detect t(5;14) involving HOX11L2 or CSX in T-cell acute lymphoblastic leukemia. | van Zutven LJ et al |
Other Information
Locus ID:
NCBI: 64919
MIM: 606558
HGNC: 13222
Ensembl: ENSG00000127152
Variants:
dbSNP: 64919
ClinVar: 64919
TCGA: ENSG00000127152
COSMIC: BCL11B
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37956270 | 2024 | The function of BCL11B in base excision repair contributes to its dual role as an oncogene and a haplo-insufficient tumor suppressor gene. | 1 |
| 38495886 | 2024 | A Bcl11b(N797K) variant isolated from an immunodeficient patient inhibits early thymocyte development in mice. | 0 |
| 38829888 | 2024 | Association between BCL11B gene polymorphisms and age-related hearing loss in the elderly: A case-control study in Qingdao, China. | 0 |
| 37956270 | 2024 | The function of BCL11B in base excision repair contributes to its dual role as an oncogene and a haplo-insufficient tumor suppressor gene. | 1 |
| 38495886 | 2024 | A Bcl11b(N797K) variant isolated from an immunodeficient patient inhibits early thymocyte development in mice. | 0 |
| 38829888 | 2024 | Association between BCL11B gene polymorphisms and age-related hearing loss in the elderly: A case-control study in Qingdao, China. | 0 |
| 37737560 | 2023 | BCL11B and the NuRD complex cooperatively guard T-cell fate and inhibit OPA1-mediated mitochondrial fusion in T cells. | 1 |
| 37986346 | 2023 | Differential expression of BCL11b and CDKN2A in CD30-positive peripheral T cell lymphoma: Retrospective study. | 0 |
| 37737560 | 2023 | BCL11B and the NuRD complex cooperatively guard T-cell fate and inhibit OPA1-mediated mitochondrial fusion in T cells. | 1 |
| 37986346 | 2023 | Differential expression of BCL11b and CDKN2A in CD30-positive peripheral T cell lymphoma: Retrospective study. | 0 |
| 34738838 | 2022 | Diagnostic challenge of identifying cases with recurrent t(8;14)(q24.21;q32.2) Involving BCL11B in acute leukemias of ambiguous lineage: an analysis of eight patients. | 0 |
| 35421541 | 2022 | Oncogenic isoform switch of tumor suppressor BCL11B in adult T-cell leukemia/lymphoma. | 1 |
| 35864006 | 2022 | Expression pattern and diagnostic utility of BCL11B in mature T- and NK-cell neoplasms. | 1 |
| 36202297 | 2022 | A de novo BCL11B variant case manifesting with dystonic movement disorder regarding the article "BCL11B-related disorder in two canadian children: Expanding the clinical phenotype (Prasad et al., 2020).". | 3 |
| 36211334 | 2022 | Decreased TCF1 and BCL11B expression predicts poor prognosis for patients with chronic lymphocytic leukemia. | 2 |
Citation
Roderick A F MacLeod ; Stefan Nagel
BCL11B (B-cell lymphoma/leukaemia 11B)
Atlas Genet Cytogenet Oncol Haematol. 2004-07-01
Online version: http://atlasgeneticsoncology.org/gene/392/bcl11b-(b-cell-lymphoma-leukaemia-11b)
