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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 |
| 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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