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

C. G. Begley, P. D. Aplan, M. P. Davey, K. Nakahara, K. Tchorz, J. Kurtzberg, M. S. Hershfield, B. F. Haynes, D. I. Cohen, T. A. Waldmann, I. R. Kirsch

Research output: Contribution to journalArticle

209 Scopus citations

Abstract

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 D(δ1) and D(δ2) was observed on derivative chromosome 1[der(1)] and D(δ1) on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the D(δ1)-D(δ2) 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.

Original languageEnglish (US)
Pages (from-to)2031-2035
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number6
DOIs
StatePublished - Jan 1 1989

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