The 5' non-coding region of the BCR/ABL oncogene augments its ability to stimulate the growth of immature lymphoid cells.
The Philadelphia chromosome (Ph1, t9:22;34:q11) is a reciprocal translocation between chromosome 22 and chromosome 9 which results in the formation of the chimeric BCR/ABL oncogene. Alternative forms of BCR/ABL are produced by splicing different sets of exons of the BCR gene to a common set of c-ABL sequences. This results in the formation of an 8.7 kilobase mRNA that encodes the P210 BCR/ABL gene product or a 7.0 kilobase mRNA that encodes the P185 BCR/ABL gene product. Both BCR/ABL transcripts derive their 5' non-coding sequences from the BCR gene locus. This 5' region is over 500 nucleotides in length, has a GC content greater than 75% and has a short open reading frame. To determine if this unusual 5' non-coding region plays a role in BCR/ABL transformation, we prepared retroviral vectors containing identical BCR/ABL coding regions but differing in the length of the BCR 5' non-coding region. Matched viral stocks were evaluated for their ability to transform bone marrow in vitro and for their ability to cause tumors when inoculated into 3- to 4-week-old mice. In this report we present the unexpected finding that the BCR/ABL 5' non-coding region augments the transforming activity of both P210 and P185 BCR/ABL in vitro. In vivo, BCR/ABL is a weak tumorigenic agent and its potency is enhanced by the presence of the 5' non-coding region.
Gishizky
M L
ML
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1570.
McLaughlin
J
J
Pendergast
A M
AM
Witte
O N
ON
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D016313:Genes, abl / Q000235:genetics*; D008221:Lymphoid Tissue / Q000166:cytology* / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010641:Phenotype; D013160:Splenic Neoplasms / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000473:pathology
D016044:Fusion Proteins, bcr-abl