Chromosomal Translocation in a Human Leukemic Stem-Cell Line Disrupts the T-Cell Antigen Receptor δ -Chain Diversity Region and Results in a Previously Unreported Fusion Transcript

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-03, Vol.86 (6), p.2031-2035
• Main Authors: Begley, C. G., Aplan, P. D., Davey, M. P., Nakahara, K., Tchorz, K., Kurtzberg, J., Hershfield, M. S., Haynes, B. F., Cohen, D. I., Waldmann, T. A., Kirsch, I. R.
• Format: Article
• Language: English
• Subjects: 550401 - Genetics- Tracer Techniques; Amino Acid Sequence; ANIMAL CELLS; ANTIGENS; Base Sequence; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; Bone Marrow - analysis; CELL DIFFERENTIATION; Cell lines; Cell receptors; Cell structures and functions; CHROMOSOMAL ABERRATIONS; Chromosome Deletion; CHROMOSOMES; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 14; Cloning, Molecular; CONNECTIVE TISSUE CELLS; DNA; DNA - genetics; DNA HYBRIDIZATION; DNA Probes; Fundamental and applied biological sciences. Psychology; GENES; Genetic loci; HETEROCHROMOSOMES; Humans; HYBRIDIZATION; HYDROGEN COMPOUNDS; KARYOTYPE; Karyotyping; Leukemia; Leukemia, Lymphoid - genetics; Leukemia, Lymphoid - immunology; Leukemia, Myeloid - genetics; Leukemia, Myeloid - immunology; LEUKOCYTES; LYMPHOCYTES; MATERIALS; MEMBRANE PROTEINS; Molecular and cellular biology; Molecular Sequence Data; MUTATIONS; Nucleic Acid Hybridization; ONCOGENES; ORGANIC COMPOUNDS; PROTEINS; RECEPTORS; Receptors, Antigen, T-Cell - genetics; RNA; RNA - analysis; SOMATIC CELLS; STEM CELLS; Stem Cells - immunology; T cell antigen receptors; TRANSCRIPTION; Transcription, Genetic; Translocation, Genetic; TRITIUM COMPOUNDS; TUMOR CELLS; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.6.2031

We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initial screening used joining (J)-segment probes from the T-cell receptor (TCR) α - and δ -chain loci. In apparent concert with the translocation, a deletion has occurred between δ -chain diversity (D)-region genes Dδ 1 and Dδ 2. Dδ 2 was observed on derivative chromosome 1 [der(1)] and Dδ 1 on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the Dδ 1-Dδ 2 deletional event implicates a lymphoid recombinase in the mechanism of the translocation. As a consequence of the translocation, an unusual fusion transcript was generated. Probes from chromosome 1 detected a previously unreported transcript in RNA from both the cell line and the patient. A chromosome 14 probe identified the same transcript, thus confirming a fusion transcript derived from both chromosomes 1 and 14. This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.