The Chronic Myelogenous Leukemia-Specific P210 Protein Is the Product of the bcr / abl Hybrid Gene

Abstract

Chronic myelogenous leukemia (CML) is a human disease associated with a consistent chromosomal translocation that results in sequences from the c- abl locus on chromosome 9 being fused to sequences in a breakpoint cluster region ( bcr ) on chromosome 22. CML cells have two novel products: an 8.5-kilobase RNA transcript containing both abl and bcr and a 210-kilodalton phosphoprotein (P210) recognized by v- abl -specific antisera. To test whether the P210 is the product of the novel 8.5-kilobase bcr / abl fusion transcript, antibodies were prepared against c- abl and bcr determinants. By using these reagents and v- abl -specific antisera, it was demonstrated that the P210 in CML cells is indeed the protein product of the 8.5-kilobase transcript. By analogy to the gag / abl fusion protein of Abelson murine leukemia virus, the replacement of amino terminal c- abl sequences by bcr sequences in P210 may create a transforming protein involved in CML. A 190-kilodalton phosphoprotein that is a candidate for the normal bcr protein was identified in both HeLa and K562 cells.