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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 (Hugo) BCL11B
Location 14q32.2
Location_base_pair Starts at 98705378 and ends at 98807575 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 
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
HGNC (Hugo)BCL11B   13222
Entrez_Gene (NCBI)BCL11B  64919  B-cell CLL/lymphoma 11B (zinc finger protein)
Cards
AtlasBCL11BID392
GeneCards (Weizmann)BCL11B
Ensembl (Hinxton)ENSG00000127152 [Gene_View]  BCL11B [Vega]
AceView (NCBI)BCL11B
Genatlas (Paris)BCL11B
euGene (Indiana)64919
SOURCE (Stanford)NM_022898 NM_138576
Genomic and cartography
GoldenPath (UCSC)BCL11B  -  14q32.2   chr14:98705378-98807575 -  14q32   [Description]    (hg18-Mar_2006)
EnsemblBCL11B - 14q32 [CytoView]
Mapping of homologs : NCBIBCL11B [Mapview]
OMIM606558   
Gene and transcription
Gene : Genbank (Entrez)AB043584 AF086271 AJ404614 BC156139
Reference sequence (RefSeq transcript) :SRSNM_022898 NM_138576
Reference transcript : EntrezNM_022898 NM_138576
RefSeq genomic : SRSAC_000057 AC_000146 NC_000014 NT_026437 NW_001838115 NW_925561
RefSeq genomic : EntrezAC_000057 AC_000146 NC_000014 NT_026437 NW_001838115 NW_925561
Consensus coding sequences : CCDS NCBIBCL11B
Cluster EST : UnigeneHs.709690 [ SRS ] Hs.709690 [ NCBI ]
Alternative Splicing : Fast-db (Paris)5545
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ9C0K0 (SRS) Q9C0K0 (Expasy) Q9C0K0 (Uniprot)
With graphics : InterProQ9C0K0
Splice isoforms : VarSplice FASTAQ9C0K0(VarSplice FASTA)
Domaine pattern : Prosite (SRS)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domain pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (SRS)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Related proteins : CluSTrQ9C0K0
Domain families : Pfam SRSzf-C2H2 (PF00096)   
Domain families : Pfam Sangerzf-C2H2 (PF00096)   
Domain families : Pfam NCBIpfam00096   
Domain families : Smart EMBLZnF_C2H2 (SM00355)
Domain structure : Prodom (Prabi Lyon)Znf_C2H2 (PD000003)   
Blocks (Seattle)Q9C0K0
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD05950
Protein Interaction databases
DIP (DOE-UCLA)Q9C0K0
IntAct (EBI)Q9C0K0
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIBCL11B
SNP : GeneSNP UtahBCL11B
SNP : HGBaseBCL11B
Genetic variants : HAPMAPBCL11B
Somatic Mutations in Cancer : COSMICBCL11B 
Translocation Breakpoints in Cancer : TICdbBCL11B 
Mutations and Diseases : HGMDBCL11B
Hereditary diseases : OMIM606558   
Hereditary diseases : GENETests606558   
Diseases : Genetic AssociationBCL11B
General knowledge
Homologs : HomoloGeneBCL11B
Homology/Alignments : Family Browser UCSCBCL11B
Phylogenetic Trees/Animal Genes : TreeFamBCL11B
Chemical/Protein Interactions : CTD64919
Keywords Ontology : AmiGOnucleic acid binding  intracellular  nucleus  transcription  regulation of transcription, DNA-dependent  zinc ion binding  metal ion binding  
Keywords Ontology : EGO-EBInucleic acid binding  intracellular  nucleus  transcription  regulation of transcription, DNA-dependent  zinc ion binding  metal ion binding  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesBCL11B Related clones (RZPD - Berlin)
Literature
PubMed16 Pubmed reference(s) in Entrez
PubGeneBCL11B

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.
Bernard OA, Busson-LeConiat M, Ballerini P, Mauchauffˆ© 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
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The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.
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Blood. 2001 ; 98 (12) : 3413-3420.
PMID 11719382
 
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
Genes, chromosomes & cancer. 2003 ; 37 (1) : 84-91.
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
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.
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PMID 12692243
 
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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Biochemical and biophysical research communications. 2003 ; 301 (2) : 598-603.
PMID 12565905
 
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
 
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.
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
Blood. 2004 ; 103 (2) : 442-450.
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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
 
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.
Togashi T, Obata M, Aoyagi Y, Kominami R, Mishima Y
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.
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
 
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

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indexed on : Sat Jun 27 16:39:03 CEST 2009

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