Molecular cloning and serological characterization of an altered c-abl gene product produced in Ph1 CML patients.

Abstract

The reciprocal translocation between human chromosomes 9 and 22, termed the Philadelphia chromosome (Ph1), is observed in more than 90% of patients with chronic myelogenous leukemia. This translocation fuses sequences from a variable distance 5' to the c-abl locus on chromosome 9 to sequences in a breakpoint cluster region (bcr) on chromosome 22. The appearance of the Ph1 chromosome is correlated with the production of a novel 8.7-kb RNA transcript containing both bcr and c-abl sequences as well as with a 210-kd phosphoprotein (p210c-abl) representing non-abl polypeptide sequences fused to c-abl-derived sequences. Antibodies prepared to a number of different c-abl domains and to bcr determinants were employed to characterize the normal and altered c-abl gene products. By combining a variety of cDNA cloning techniques, we have isolated bcr/abl clones representing 8.7 kb of contiguous mRNA sequence.