Juxtaposition of the T-Cell Receptor α -Chain Locus (14q11) and a Region (14q32) of Potential Importance in Leukemogenesis by a 14;14 Translocation in a Patient with T-Cell Chronic Lymphocytic Leukemia and Ataxia-Telangiectasia

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 85; no. 23; pp. 9287 - 9291
• Main Authors: Davey, Michael P., Bertness, Virginia, Nakahara, Kenneth, Johnson, John P., McBride, O. Wesley, Waldmann, Thomas A., Kirsch, Ilan R.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-12-1988; National Acad Sciences
• Subjects: Ataxia Telangiectasia - complications; Ataxia Telangiectasia - genetics; Ataxia Telangiectasia - immunology; Bacteriophages; Base Sequence; Biological and medical sciences; Blotting, Southern; Cells, Cultured; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 14; Chronic lymphocytic leukemia; DNA; DNA probes; Genes; Genetic loci; Granulocytes - immunology; Hematologic and hematopoietic diseases; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - complications; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, T-Cell - complications; Leukemia, T-Cell - genetics; Leukemia, T-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes - immunology; Medical sciences; Molecular Sequence Data; Receptors, Antigen, T-Cell - genetics; T cell antigen receptors; T lymphocytes; Translocation, Genetic; Tumors; Leukemia; T-Lymphocyte
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.23.9287

We describe a t(14;14)(q11;q32) translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia (AT). By using a battery of joining (J)-segment probes from the T-cell receptor (TCR) α -chain locus TCRA, three distinct Jα rearrangements were observed. One rearrangement reflected a normal TCRA variable (V) region Vα-to-Jα recombination. The second rearrangement was caused by the translocation event itself, which joined a DNA segment from 14q32 centromeric to the immunoglobulin heavy chain locus (IGH) and a Jα gene located ≈ 75 kilobases (kb) 5′ of the TCRA constant region gene (Cα). A third rearrangement involved a 17-kb internal deletion 3′ to the translocation, a rearrangement within the Jα locus that has been observed once before in a patient with AT. Analysis of these three rearrangements underscores the increase in aberrant locus-specific recombination in lymphocytes from patients with AT. Furthermore, these studies support the view that a growth-effecting gene is present in the 14q32 region that participates in the leukemogenic process.