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.
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.
Bernards
A
A
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Rubin
C M
CM
Westbrook
C A
CA
Paskind
M
M
Baltimore
D
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D004587:Electrophoresis, Agar Gel; D005796:Genes; D006801:Humans; D007438:Introns; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D010677:Philadelphia Chromosome; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins