Expression of a translocated c-abl gene in hybrids of mouse fibroblasts and chronic myelogenous leukaemia cells

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Abstract
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 transcripts6–9 and to express the normal p145 abl protein and a p210 c-abl protein possessing a tyrosine kinase activity not detected in the p145 species10–12. 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.