Bernards, André and Rubin, Charles M. and Westbrook, Carol A. and Paskind, Michael and Baltimore, David (1987) The first intron in the human c-abl gene is at least 200 kilobases long and is a target for translocations in chronic myelogenous leukemia. Molecular and Cellular Biology, 7 (9). pp. 3231-3236. ISSN 0270-7306 http://resolver.caltech.edu/CaltechAUTHORS:BERmcb87
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The c-abl protooncogene is unusual in two respects; it has multiple, widely space N-terminal coding exons transcribed by different promoters, and it is the target of the translocations that form the Philadelphia chromosome found in cells of chronic myelogenous leukemia patients. To understand the organization of the gene in normal and chronic myelogenous leukemia patient DNA we have mapped c-abl by pulsed field gradient gel electrophoresis. We find that one of the alternative 5' exons of the gene lies at least 200 kilobases upstream of the remaining c-abl exons, posing formidable transcription and splicing problems. The 5'-most c-abl exon includes an unusually long 1,276-base-pair segment that contains 15 ATG codons and multiple short open reading frames, upstream of the abl initiator codon. Its peculiar structure suggests that c-abl may be decapitated in most chronic myelogenous leukemia patients, and we demonstrate that this is the case in the chronic myelogenous leukemia cell line K562.
|Additional Information:||Copyright © 1987 by the American Society for Microbiology. Received 13 April 1987/Accepted 11 June 1987. We thank Janet Rowley and Gerard Grosveld for helpful discussion and advice and Gerard Grosveld and John Groffen for the A28-2-2, BBO.9, T39-1-2, and T39-2-2 probes. We also thank Nathaniel Landau for the human recombinant library. This work was supported by Public Health Service program project grant CA 38497 from the National Cancer Institute to D.B., by Public Health Service grant GM 07190 to C.M.R. from the National Institutes of Health, and by grants from the American Cancer Society, Illinois division, and the University of Chicago Research Foundation to C.A.W. A.B. is supported by the European Molecular Biology Organization. C.A.W. is a Stratton-Jaffe Fellow of the American Society of Hematology.|
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