title: Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) is associated with chromosomal aberrations characterized by juxtaposition of proto-oncogenes to T-cell receptor gene loci (TCR), resulting in the deregulated transcription of these proto-oncogenes. Here, we describe the molecular characterization of a novel chromosomal aberration, inv(14)(q11.2q32.31), in a T-ALL sample, involving the recently described BCL11B gene and the TCRD locus. The inversion joined the 5' part of BCL11B, including exons 1-3, to the TRDD3 gene segment of the TCRD locus, whereas the reciprocal breakpoint fused the TRDV1 gene segment to the fourth exon of BCL11B. The TRDV1-BCL11B joining region was 1344 bp long and contained fragments derived from 20q11.22, 3p21.33 and from 11p12, indicating the complex character of this aberration. A strong expression of in-frame transcripts with truncated BCL11B and TCRD constant region (TRDC) were observed, but in contrast to normal T cells and other T-ALL samples, no wild-type BCL11B transcripts were detected in the T-ALL sample. Screening of 37 other T-ALLs revealed one additional case with expression of the BCL11B-TRDC fusion transcript. As BCL11B appears to play a key role in T-cell differentiation, BCL11B disruption and disturbed expression may contribute to the development of T-cell malignancies in man.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. przybylg@man.poznan.pl
authors.forename: G K
authors.initials: GK
authors.lastname: Przybylski
authors.forename: W A
authors.initials: WA
authors.lastname: Dik
authors.forename: J
authors.initials: J
authors.lastname: Wanzeck
authors.forename: P
authors.initials: P
authors.lastname: Grabarczyk
authors.forename: S
authors.initials: S
authors.lastname: Majunke
authors.forename: J I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: R
authors.initials: R
authors.lastname: Siebert
authors.forename: G
authors.initials: G
authors.lastname: Dölken
authors.forename: W-D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: B
authors.initials: B
authors.lastname: Verhaaf
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: C A
authors.initials: CA
authors.lastname: Schmidt
authors.forename: A W
authors.initials: AW
authors.lastname: Langerak
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
chemical_list: C479740:BCL11B protein, human; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins