title: The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.
abstract: Many malignancies of mature B cells are characterized by chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus on chromosome 14q32.3 and result in deregulated expression of the translocated oncogene. t(2;14)(p13;q32.3) is a rare event in B-cell malignancies. In contrast, gains and amplifications of the same region of chromosome 2p13 have been reported in 20% of extranodal B-cell non-Hodgkin lymphomas (B-NHL), in follicular and mediastinal B-NHL, and in Hodgkin disease (HD). It has been suggested that REL, an NF-kappaB gene family member, mapping within the amplified region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krüppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14)(p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene (BCL11B) on chromosome 14q32.1. BCL11A coamplified with REL in B-NHL cases and HD lymphoma cell lines with gains and amplifications of 2p13, suggesting that BCL11A may be involved in lymphoid malignancies through either chromosomal translocation or amplification.
authors.affiliation: Academic Department of Haematology and Cytogenetics, Haddow Laboratories, Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Satterwhite
authors.forename: T
authors.initials: T
authors.lastname: Sonoki
authors.forename: T G
authors.initials: TG
authors.lastname: Willis
authors.forename: L
authors.initials: L
authors.lastname: Harder
authors.forename: R
authors.initials: R
authors.lastname: Nowak
authors.forename: E L
authors.initials: EL
authors.lastname: Arriola
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: H P
authors.initials: HP
authors.lastname: Price
authors.forename: S
authors.initials: S
authors.lastname: Gesk
authors.forename: D
authors.initials: D
authors.lastname: Steinemann
authors.forename: B
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: D G
authors.initials: DG
authors.lastname: Oscier
authors.forename: R
authors.initials: R
authors.lastname: Siebert
authors.forename: P W
authors.initials: PW
authors.lastname: Tucker
authors.forename: M J
authors.initials: MJ
authors.lastname: Dyer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins; D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007938:Leukemia / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D009687:Nuclear Proteins; D012313:RNA / Q000032:analysis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D012313:RNA