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BCL11B (B-cell lymphoma/leukaemia 11B)

Written2004-07Roderick A F MacLeod, Stefan Nagel
DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen, Mascheroder Weg 1b 38124, Braunschweig, Germany

(Note : for Links provided by Atlas : click)

Identity

Other namesCTIP2 (Ctip-2) chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein
Rit1 zinc finger protein hRit1 alpha (not to be confused with RIT1 on chr. 1q22)
HGNC (Hugo) BCL11B
LocusID (NCBI) 64919
Atlas_Id 392
Location 14q32.2  [Link to chromosome band 14q32]
Location_base_pair Starts at 99635625 and ends at 99738050 bp from pter ( according to hg19-Feb_2009)  [Mapping BCL11B.png]
 
Fusion genes
(updated 2016)
BCL11B (14q32.2) / AMOT (Xq23)BCL11B (14q32.2) / BCL11B (14q32.2)BCL11B (14q32.2) / MICB (6p21.33)
BCL11B (14q32.2) / NKX2-5 (5q35.1)BCL11B (14q32.2) / TLX3 (5q35.1)BCL11B (14q32.2) / TRA ()
BCL11B (14q32.2) / TRBV20OR9-2 ()BCL11B (14q32.2) / TRD ()IKZF2 (2q34) / BCL11B (14q32.2)
Ig () / BCL11B (14q32.2)MICB (6p21.33) / BCL11B (14q32.2)RNA28S5 () / BCL11B (14q32.2)
TLX3 (5q35.1) / BCL11B (14q32.2)
Note BCL11B (14q32.2): FISH with RP11 BAC clones 1127d7 (green label) and 1057p17 (red label) showing split signal as indicated above right (dotted lines). Observe telomeric part of chr 14 translocated to the der(5) as revealed by the red doublet signal. The der(14) partner in turn receives a microinsertion containing material from chr 5. Analysis was performed on the pediatric T-ALL cell line CCRF-CEM which carries t(5;14)(q35.1;q32) resulting in ectopic expression of of NKX2-5 (2Mbp telomeric of, and closely related to, the standard partner gene TLX3 at 5q35) by juxtaposition with the far downstream region of BCL11B.

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.

Protein

 
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

Note
Entity T-cell acute lymphoblastic leukemia (T-ALL) with t(5;14)(q35;q32) --> TLX3 - BCL11B
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.

Bibliography

COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein.
Avram D, Fields A, Senawong T, Topark-Ngarm A, Leid M
The Biochemical journal. 2002 ; 368 (Pt 2) : 555-563.
PMID 12196208
 
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, Busson-LeConiat M, Ballerini P, Mauchauffé M, Della Valle V, Monni R, Nguyen Khac F, Mercher T, Penard-Lacronique V, Pasturaud P, Gressin L, Heilig R, Daniel MT, Lessard M, Berger R
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (10) : 1495-1504.
PMID 11587205
 
A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene.
Bezrookove V, van Zelderen-Bhola SL, Brink A, Szuhai K, Raap AK, Barge R, Beverstock GC, Rosenberg C
Cancer genetics and cytogenetics. 2004 ; 149 (1) : 72-76.
PMID 15104287
 
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, Suciu S, Preudhomme C, Poppe B, Robert A, Uyttebroeck A, Malet M, Boutard P, Benoit Y, Mauvieux L, Lutz P, Méchinaud F, Grardel N, Mazingue F, Dupont M, Margueritte G, Pages MP, Bertrand Y, Plouvier E, Brunie G, Bastard C, Plantaz D, Vande Velde I, Hagemeijer A, Speleman F, Lessard M, Otten J, Vilmer E, EORTC-CLG, Dastugue N
Blood. 2004 ; 103 (2) : 442-450.
PMID 14504110
 
Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites.
Crawford GE, Holt IE, Mullikin JC, Tai D, Blakesley R, Bouffard G, Young A, Masiello C, Green ED, Wolfsberg TG, National Institutes Of Health Intramural Sequencing Center, Collins FS
Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (4) : 992-997.
PMID 14732688
 
BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia.
MacLeod RA, Nagel S, Drexler HG
Cancer genetics and cytogenetics. 2004 ; 153 (1) : 88-89.
PMID 15325104
 
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, Kaufmann M, Drexler HG, MacLeod RA
Cancer research. 2003 ; 63 (17) : 5329-5334.
PMID 14500364
 
Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells.
Rohr O, Lecestre D, Chasserot-Golaz S, Marban C, Avram D, Aunis D, Leid M, Schaeffer E
Journal of virology. 2003 ; 77 (9) : 5415-5427.
PMID 12692243
 
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, Inoue J, Ohi H, Kosugi-Okano H, Mishima Y, Hatakeyama K, Niwa O, Kominami R
Carcinogenesis. 2004 ; 25 (6) : 1069-1075.
PMID 14754877
 
The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.
Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ
Blood. 2001 ; 98 (12) : 3413-3420.
PMID 11719382
 
Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression.
Senawong T, Peterson VJ, Avram D, Shepherd DM, Frye RA, Minucci S, Leid M
The Journal of biological chemistry. 2003 ; 278 (44) : 43041-43050.
PMID 12930829
 
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, Obata M, Aoyagi Y, Kominami R, Mishima Y
Biochemical and biophysical research communications. 2004 ; 313 (3) : 489-495.
PMID 14697215
 
Bcl11b is required for differentiation and survival of alphabeta T lymphocytes.
Wakabayashi Y, Watanabe H, Inoue J, Takeda N, Sakata J, Mishima Y, Hitomi J, Yamamoto T, Utsuyama M, Niwa O, Aizawa S, Kominami R
Nature immunology. 2003 ; 4 (6) : 533-539.
PMID 12717433
 
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, Velthuizen SC, Wolvers-Tettero IL, van Dongen JJ, Poulsen TS, MacLeod RA, Beverloo HB, Langerak AW
Haematologica. 2004 ; 89 (6) : 671-678.
PMID 15194534
 

Citation

This paper should be referenced as such :
MacLeod, RAF ; Nagel, S
BCL11B (B-cell lymphoma/leukaemia 11B)
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):228-231.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BCL11BID392.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 5 ]
  t(2;14)(p13-16;q32) IGH/BCL11A
t(5;14)(q35;q32) BCL11B/TLX3
t(5;14)(q35;q32.2) BCL11B/TLX3 and NKX2-5
t(6;14)(q25-27;q32) BCL11B/?
T-lineage acute lymphoblastic leukemia (T-ALL)

External links

Nomenclature
HGNC (Hugo)BCL11B   13222
Cards
AtlasBCL11BID392
Entrez_Gene (NCBI)BCL11B  64919  B-cell CLL/lymphoma 11B
AliasesATL1; ATL1-alpha; ATL1-beta; ATL1-delta; 
ATL1-gamma; CTIP-2; CTIP2; RIT1; ZNF856B; hRIT1-alpha
GeneCards (Weizmann)BCL11B
Ensembl hg19 (Hinxton)ENSG00000127152 [Gene_View]  chr14:99635625-99738050 [Contig_View]  BCL11B [Vega]
Ensembl hg38 (Hinxton)ENSG00000127152 [Gene_View]  chr14:99635625-99738050 [Contig_View]  BCL11B [Vega]
ICGC DataPortalENSG00000127152
TCGA cBioPortalBCL11B
AceView (NCBI)BCL11B
Genatlas (Paris)BCL11B
WikiGenes64919
SOURCE (Princeton)BCL11B
Genomic and cartography
GoldenPath hg19 (UCSC)BCL11B  -     chr14:99635625-99738050 -  14q32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)BCL11B  -     14q32   [Description]    (hg38-Dec_2013)
EnsemblBCL11B - 14q32 [CytoView hg19]  BCL11B - 14q32 [CytoView hg38]
Mapping of homologs : NCBIBCL11B [Mapview hg19]  BCL11B [Mapview hg38]
OMIM606558   
Gene and transcription
Genbank (Entrez)AB041218 AB043584 AB057668 AB057669 AB057670
RefSeq transcript (Entrez)NM_001282237 NM_001282238 NM_022898 NM_138576
RefSeq genomic (Entrez)NC_000014 NC_018925 NG_027894 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)BCL11B
Cluster EST : UnigeneHs.709690 [ NCBI ]
CGAP (NCI)Hs.709690
Alternative Splicing GalleryENSG00000127152
Gene ExpressionBCL11B [ NCBI-GEO ]   BCL11B [ EBI - ARRAY_EXPRESS ]   BCL11B [ SEEK ]   BCL11B [ MEM ]
Gene Expression Viewer (FireBrowse)BCL11B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)64919
GTEX Portal (Tissue expression)BCL11B
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9C0K0 (Uniprot)
NextProtQ9C0K0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9C0K0
Splice isoforms : SwissVarQ9C0K0 (Swissvar)
PhosPhoSitePlusQ9C0K0
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)zf-C2H2 (PF00096)   
Domain families : Pfam (NCBI)pfam00096   
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
DMDM Disease mutations64919
Blocks (Seattle)BCL11B
SuperfamilyQ9C0K0
Human Protein AtlasENSG00000127152
Peptide AtlasQ9C0K0
HPRD05950
IPIIPI00009213   IPI00009646   IPI00853567   
Protein Interaction databases
DIP (DOE-UCLA)Q9C0K0
IntAct (EBI)Q9C0K0
FunCoupENSG00000127152
BioGRIDBCL11B
STRING (EMBL)BCL11B
ZODIACBCL11B
Ontologies - Pathways
QuickGOQ9C0K0
Ontology : AmiGORNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  keratinocyte development  epithelial cell morphogenesis  protein binding  nucleus  transcription from RNA polymerase II promoter  signal transduction  negative regulation of cell proliferation  regulation of keratinocyte proliferation  regulation of lipid metabolic process  striatal medium spiny neuron differentiation  commitment of neuronal cell to specific neuron type in forebrain  neurogenesis  post-embryonic camera-type eye development  T cell differentiation in thymus  T cell receptor V(D)J recombination  odontogenesis of dentin-containing tooth  neuron projection  negative regulation of apoptotic process  positive T cell selection  sequence-specific DNA binding  transcription regulatory region DNA binding  regulation of neuron differentiation  positive regulation of transcription from RNA polymerase II promoter  alpha-beta T cell differentiation  metal ion binding  thymus development  olfactory bulb axon guidance  
Ontology : EGO-EBIRNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  keratinocyte development  epithelial cell morphogenesis  protein binding  nucleus  transcription from RNA polymerase II promoter  signal transduction  negative regulation of cell proliferation  regulation of keratinocyte proliferation  regulation of lipid metabolic process  striatal medium spiny neuron differentiation  commitment of neuronal cell to specific neuron type in forebrain  neurogenesis  post-embryonic camera-type eye development  T cell differentiation in thymus  T cell receptor V(D)J recombination  odontogenesis of dentin-containing tooth  neuron projection  negative regulation of apoptotic process  positive T cell selection  sequence-specific DNA binding  transcription regulatory region DNA binding  regulation of neuron differentiation  positive regulation of transcription from RNA polymerase II promoter  alpha-beta T cell differentiation  metal ion binding  thymus development  olfactory bulb axon guidance  
NDEx NetworkBCL11B
Atlas of Cancer Signalling NetworkBCL11B
Wikipedia pathwaysBCL11B
Orthology - Evolution
OrthoDB64919
GeneTree (enSembl)ENSG00000127152
Phylogenetic Trees/Animal Genes : TreeFamBCL11B
Homologs : HomoloGeneBCL11B
Homology/Alignments : Family Browser (UCSC)BCL11B
Gene fusions - Rearrangements
Fusion : MitelmanBCL11B/NKX2-5 [14q32.2/5q35.1]  
Fusion : MitelmanBCL11B/TLX3 [14q32.2/5q35.1]  [t(5;14)(q35;q32)]  
Fusion : MitelmanBCL11B/TRD [14q32.2/-]  [inv(14)(q11q32)]  
Fusion : MitelmanIKZF2/BCL11B [2q34/14q32.2]  [t(2;14)(q34;q32)]  
Fusion : MitelmanRNA28S5/BCL11B [-/14q32.2]  [t(X;14)(q22;q32)]  
Fusion : TICdbBCL11B [14q32.2]  -  TCR []
Fusion : TICdbIKZF2 [2q34]  -  BCL11B [14q32.2]
Fusion : TICdbIg [BCL11B]  -  14q32.2 []
Polymorphisms : SNP, variants
NCBI Variation ViewerBCL11B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BCL11B
dbVarBCL11B
ClinVarBCL11B
1000_GenomesBCL11B 
Exome Variant ServerBCL11B
ExAC (Exome Aggregation Consortium)BCL11B (select the gene name)
Genetic variants : HAPMAP64919
Genomic Variants (DGV)BCL11B [DGVbeta]
Mutations
ICGC Data PortalBCL11B 
TCGA Data PortalBCL11B 
Broad Tumor PortalBCL11B
OASIS PortalBCL11B [ Somatic mutations - Copy number]
Cancer Gene: CensusBCL11B 
Somatic Mutations in Cancer : COSMICBCL11B 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch BCL11B
DgiDB (Drug Gene Interaction Database)BCL11B
DoCM (Curated mutations)BCL11B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BCL11B (select a term)
intoGenBCL11B
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:99635625-99738050  ENSG00000127152
CONAN: Copy Number AnalysisBCL11B 
Mutations and Diseases : HGMDBCL11B
OMIM606558   
MedgenBCL11B
Genetic Testing Registry BCL11B
NextProtQ9C0K0 [Medical]
TSGene64919
GENETestsBCL11B
Huge Navigator BCL11B [HugePedia]
snp3D : Map Gene to Disease64919
BioCentury BCIQBCL11B
ClinGenBCL11B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD64919
Chemical/Pharm GKB GenePA25301
Clinical trialBCL11B
Miscellaneous
canSAR (ICR)BCL11B (select the gene name)
Probes
Litterature
PubMed49 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBCL11B
EVEXBCL11B
GoPubMedBCL11B
iHOPBCL11B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Sep 28 15:56:03 CEST 2016

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