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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 aliasCTIP2 (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)
LocusID (NCBI) 64919
Atlas_Id 392
Location 14q32.2  [Link to chromosome band 14q32]
Location_base_pair Starts at and ends at bp from pter
 
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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) / TRBV20OR9-2 (-)
CEP83 (12q22) / BCL11B (14q32.2)IKZF2 (2q34) / BCL11B (14q32.2)MICB (6p21.33) / BCL11B (14q32.2)
STPG1 (1p36.11) / BCL11B (14q32.2)TLX3 (5q35.1) / BCL11B (14q32.2)ZEB2 (2q22.3) / 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) [ 26 ]
  Pediatric T-Cell Acute Lymphoblastic Leukemia
t(6;14)(q25-27;q32) BCL11B/?
inv(14)(q11.2q32.31) BCL11B/TRDC
inv(14)(q11q32) BCL11B/TRD
t(2;14)(q22;q32) ZEB2/BCL11B
t(2;14)(q34;q32) IKZF2/BCL11B
t(2;14)(q34;q32) IKZF2/BCL11B
t(5;14)(q35;q32) BCL11B/NKX2-5
t(5;14)(q35;q32) TLX3/BCL11B
t(14;14)(q13;q32) NKX2-1/BCL11B
t(X;14)(q22;q32) RNA28S5/BCL11B
Pediatric T-Cell Acute Lymphoblastic Leukemia
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)
inv(14)(q11.2q32.31) BCL11B/TRDC
inv(14)(q11q32) BCL11B/TRD
t(2;14)(q22;q32) ZEB2/BCL11B
t(2;14)(q34;q32) IKZF2/BCL11B
t(2;14)(q34;q32) IKZF2/BCL11B
t(5;14)(q35;q32) BCL11B/NKX2-5
t(5;14)(q35;q32) TLX3/BCL11B
t(14;14)(q13;q32) NKX2-1/BCL11B
t(X;14)(q22;q32) RNA28S5/BCL11B


External links

Nomenclature
Cards
AtlasBCL11BID392.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)64919
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 18 17:29:29 CEST 2018

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