Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript.
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) alpha- and delta-chain loci. In apparent concert with the translocation, a deletion has occurred between delta-chain diversity (D)-region genes D delta 1 and D delta 2. D delta 2 was observed on derivative chromosome 1 [der(1)] and D delta 1 on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the D delta 1-D delta 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.
Begley
C G
CG
Navy Medical Oncology, Branche National Cancer Institute, Bethesda, MD 20892.
Aplan
P D
PD
Davey
M P
MP
Nakahara
K
K
Tchorz
K
K
Kurtzberg
J
J
Hershfield
M S
MS
Haynes
B F
BF
Cohen
D I
DI
Waldmann
T A
TA
D000595:Amino Acid Sequence; D001483:Base Sequence; D001853:Bone Marrow / Q000032:analysis; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D006801:Humans; D007621:Karyotyping; D007945:Leukemia, Lymphoid / Q000235:genetics* / Q000276:immunology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013234:Stem Cells / Q000276:immunology*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D011948:Receptors, Antigen, T-Cell; D012313:RNA; D004247:DNA