Atlas of Genetics and Cytogenetics in Oncology and Haematology


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BCL11B (B-cell lymphoma/leukaemia 11B)

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 BCL11B
Location 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

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.

External links

Nomenclature
HGNCBCL11B   13222
Entrez_GeneBCL11B  64919  B-cell CLL/lymphoma 11B (zinc finger protein)
Cards
AtlasBCL11BID392
GeneCardsBCL11B
EnsemblBCL11B [Search_View]   ENSG00000127152 [Gene_View]
GenatlasBCL11B
GeneLynxBCL11B
eGenomeBCL11B
euGene64919
Genomic and cartography
GoldenPathBCL11B  -  14q32.2   chr14:98705378-98807575 -  14q32   [Description]    (hg18-Mar_2006)
EnsemblBCL11B - 14q32 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneBCL11B
Gene and transcription
GenbankAB043584 [ ENTREZ ]
GenbankAF086271 [ ENTREZ ]
GenbankAJ404614 [ ENTREZ ]
GenbankBC156139 [ ENTREZ ]
RefSeqNM_022898 [ SRS ]    NM_022898 [ ENTREZ ]
RefSeqNM_138576 [ SRS ]    NM_138576 [ ENTREZ ]
RefSeqAC_000057 [ SRS ]    AC_000057 [ ENTREZ ]
RefSeqAC_000146 [ SRS ]    AC_000146 [ ENTREZ ]
RefSeqNC_000014 [ SRS ]    NC_000014 [ ENTREZ ]
RefSeqNT_026437 [ SRS ]    NT_026437 [ ENTREZ ]
RefSeqNW_001838115 [ SRS ]    NW_001838115 [ ENTREZ ]
RefSeqNW_925561 [ SRS ]    NW_925561 [ ENTREZ ]
AceViewBCL11B AceView - NCBI
UnigeneHs.709690 [ SRS ]    Hs.709690 [ NCBI ]     HS709690 [ spliceNest ]
Fast-db5545 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ9C0K0 [ SRS]    Q9C0K0 [ EXPASY ]     Q9C0K0 [ INTERPRO ]     Q9C0K0 [ UNIPROT ]
PrositePS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
PrositePS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
InterproIPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
InterproIPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
InterproIPR013087 Znf_C2H2/integrase_DNA-bd [ SRS ]    IPR013087 Znf_C2H2/integrase_DNA-bd [ EBI ]
CluSTrQ9C0K0
PfamPF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
SmartSM00355 ZnF_C2H2 [EMBL]
ProdomPD000003 Znf_C2H2[INRA-Toulouse]
ProdomQ9C0K0 BC11B_HUMAN [ Domain structure ]   Q9C0K0 BC11B_HUMAN  [ sequences sharing at least 1 domain ]
BlocksQ9C0K0
HPRD05950
Protein Interaction databases
DIPQ9C0K0
IntActQ9C0K0
Polymorphism : SNP, mutations, diseases
OMIM606558    [ map ]   
GENECLINICS606558
SNPBCL11B [dbSNP-NCBI]  
SNPNM_022898 [SNP-NCI]  
SNPNM_138576 [SNP-NCI]  
SNPBCL11B [GeneSNPs - Utah]  BCL11B] [HGBASE - SRS]
HAPMAPBCL11B [HAPMAP]  
COSMICBCL11B [Somatic mutation (COSMIC-CGP-Sanger)]  
TICdbBCL11B [Translocation breakpoints In Cancer]  
HGMDBCL11B
General knowledge
Family BrowserBCL11B [UCSC Family Browser]
SOURCENM_022898
SOURCENM_138576
SMDHs.709690
SAGEHs.709690
GOnucleic acid binding [Amigo]  nucleic acid binding
GOintracellular [Amigo]  intracellular
GOnucleus [Amigo]  nucleus
GOtranscription [Amigo]  transcription
GOregulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GOzinc ion binding [Amigo]  zinc ion binding
GOmetal ion binding [Amigo]  metal ion binding
PubGeneBCL11B
TreeFamBCL11B
CTD64919 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeBCL11B Related clones (RZPD - Berlin)
PubMed
PubMed14 Pubmed reference(s) in LocusLink

Bibliography

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.
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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
 
Activation of HOX11L2 by juxtaposition with 3'-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2).
MacLeod RA, Nagel S, Kaufmann M, Janssen JW, Drexler HG
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PMID 12661009
 
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
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PMID 14500364
 
Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells.
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Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression.
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The Journal of biological chemistry. 2003 ; 278 (44) : 43041-43050.
PMID 12930829
 
Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas.
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Bcl11b is required for differentiation and survival of alphabeta T lymphocytes.
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PMID 12717433
 
A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene.
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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.
Cavˆ© H, Suciu S, Preudhomme C, Poppe B, Robert A, Uyttebroeck A, Malet M, Boutard P, Benoit Y, Mauvieux L, Lutz P, Mˆ©chinaud 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
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Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites.
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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
 
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
 
Two distinct methods analyzing chromatin structure using centrifugation and antibodies to modified histone H3: both provide similar chromatin states of the Rit1/Bcl11b gene.
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Biochemical and biophysical research communications. 2004 ; 313 (3) : 489-495.
PMID 14697215
 
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.
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Haematologica. 2004 ; 89 (6) : 671-678.
PMID 15194534
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2004Roderick A F MacLeod, Stefan Nagel
DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen, Mascheroder Weg 1b 38124, Braunschweig, Germany

Citation

This paper should be referenced as such :
MacLeod RAF, Nagel S . BCL11B (B-cell lymphoma/leukaemia 11B). Atlas Genet Cytogenet Oncol Haematol. July 2004 .
URL : http://AtlasGeneticsOncology.org/Genes/BCL11BID392.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Aug 11 21:12:26 2008


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