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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
- Source :
- Journal of Experimental Medicine 177 (4): 965-977.
- Publication Year :
- 1993
- Publisher :
- Rockefeller University Press (U.S.A.), 1993.
-
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.
- Subjects :
- Cancer Research
Genetic Recombination
Base Sequence
Molecular Sequence Data
Restriction Mapping
Intracellular Signaling Peptides and Proteins
570 Life Sciences
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Polymerase Chain Reaction
610 Medical Sciences, Medicine
DNA-Binding Proteins
Phenotype
Proto-Oncogene Proteins
Basic Helix-Loop-Helix Transcription Factors
Neoplasm DNA
T-Cell Antigen Receptors
Southern Blotting
Gene Deletion
CD3 Antigens
Fusion Oncogene Proteins
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 00221007
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine 177 (4): 965-977.
- Accession number :
- edsair.mdc......med..fde38781479604f416d26caa0f7b4be2