Alpha-chain locus of the T-cell antigen receptor is involved in the t(10;14) chromosome translocation of T-cell acute lymphocytic leukemia.
Human leukemic T cells carrying a t(10;14)(q24;q11) chromosome translocation were fused with mouse leukemic T cells, and the hybrids were examined for genetic markers of human chromosomes 10 and 14. Hybrids containing the human 10q+ chromosome had the human genes for terminal deoxynucleotidyltransferase that has been mapped at 10q23-q25 and for C alpha [the constant region of TCRA (the alpha-chain locus of the T-cell antigen receptor gene)], but not for V alpha (the variable region of TCRA). Hybrids containing the human 14q- chromosome retained the V alpha genes. Thus the 14q11 breakpoint in the t(10;14) chromosome translocation directly involves TCRA, splitting the locus in a region between the V alpha and the C alpha genes. These results suggest that the translocation of the C alpha locus to a putative cellular protooncogene located proximal to the breakpoint at 10q24, for which we propose the name TCL3, results in its deregulation, leading to T-cell leukemia. Since hybrids with the 10q+ chromosome also retained the human terminal deoxynucleotidyltransferase gene, it is further concluded that the terminal deoxynucleotidyltransferase locus is proximal to the TCL3 gene, at band 10q23-q24.
D000328:Adult; D000818:Animals; D002879:Chromosomes, Human, Pair 10 / Q000648:ultrastructure*; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure*; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D006800:Deltaretrovirus Infections / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells / Q000032:analysis; D007942:Leukemia, Experimental / Q000235:genetics; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics*; D011519:Proto-Oncogenes; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014178:Translocation, Genetic
D005819:Genetic Markers; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004253:DNA Nucleotidylexotransferase