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Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes

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Item Type:Article
Title:Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes
Creators Name:Breit, T.M. and Mol, E.J. and Wolvers-Tettero, I.L. and Ludwig, W.D. and van Wering, E.R. and van Dongen, J.J.
Abstract:Site-specific deletions in the tal-1 gene are reported to occur in 12-26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T-ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion regions of the tal-1 deletion breakpoints strongly resemble the RSS and junctional regions of immunoglobulin/T cell receptor (TCR) gene rearrangements, which implies that they are probably caused by the same V(D)J recombinase complex. Analysis of the 134 T-ALL suggested that the occurrence of tal-1 deletions is associated with the CD3 phenotype, because no tal-1 deletions were found in 25 TCR-gamma/delta + T-ALL, whereas 8 of the 69 CD3- T-ALL and 11 of the 40 TCR-alpha/beta + T-ALL contained such a deletion. Careful examination of all TCR genes revealed that tal-1 deletions exclusively occurred in CD3- or CD3+ T-ALL of the alpha/beta lineage with a frequency of 18% in T-ALL with one deleted TCR-delta allele, and a frequency of 34% in T-ALL with TCR-delta gene deletions on both alleles. Therefore, we conclude that alpha/beta lineage commitment of the T-ALL and especially the extent of TCR-delta gene deletions determines the chance of a tal-1 deletion. This suggests that tal-1 deletions are mediated via the same deletion mechanism as TCR-delta gene deletions.
Keywords:CD3 Antigens, Base Sequence, Basic Helix-Loop-Helix Transcription Factors, Southern Blotting, Neoplasm DNA, DNA-Binding Proteins, Gene Deletion, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Fusion Oncogene Proteins, Phenotype, Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins, T-Cell Antigen Receptors, Genetic Recombination, Restriction Mapping, Transcription Factors
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Volume:177
Number:4
Page Range:965-977
Date:1 April 1993
Official Publication:http://www.jem.org/cgi/content/abstract/177/4/965
PubMed:View item in PubMed

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