Expression of a translocated c-abl gene in hybrids of mouse fibroblasts and chronic myelogenous leukaemia cells.
Chronic myelogenous leukaemia (CML) is a clonal disease arising from malignant transformation of pluripotent hematopoietic stem cells. In most cases, it is characterized by the presence of the Philadelphia (Ph1) chromosome (22q-) which results from a reciprocal translocation between chromosomes 9 and 22 (refs 1-3). In this translocation, the human homologue of the Abelson virus oncogene, c-abl, normally on chromosome 9, is moved to chromosome 22, while c-sis, the cellular homologue of the simian sarcoma virus oncogene, is moved from chromosome 22 to chromosome 9 (refs 4-6). CML cells carrying the t(9;22) chromosomal translocation are known to produce an 8-kilobase (kb) c-abl transcript in addition to the normal 6- and 7-kb transcripts and to express the normal p145 abl protein and a p210 c-abl protein possessing a tyrosine kinase activity not detected in the p145 species. Results of our analyses using somatic cell hybrids between a mouse fibroblast line and two human CML-derived cell lines which carry the Ph1 chromosome and are phenotypically identical to the fibroblast parent indicate that only the hybrid cells containing Ph1 chromosome express both the 8-kb c-abl RNA and the p210 protein. Thus, expression of the altered c-abl transcripts and protein depends on the presence of the Ph1 chromosome and is not myeloid-specific.
Kozbor
D
D
Giallongo
A
A
Sierzega
M E
ME
Konopka
J B
JB
Witte
O N
ON
Showe
L C
LC
Croce
C M
CM
D000818:Animals; D002906:Chromosomes, Human, 6-12 and X; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009857:Oncogenes; D010677:Philadelphia Chromosome; D014158:Transcription, Genetic; D014178:Translocation, Genetic