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

TLDR

Chronic myelogenous leukemia is driven by a recurrent translocation fusing c‑abl to bcr, producing an 8.5‑kb RNA and a 210‑kDa phosphoprotein P210 that may act as a transforming protein. The study aimed to determine whether P210 is the protein product of the 8.5‑kb bcr/abl fusion transcript. Antibodies against c‑abl and bcr domains were generated and used with v‑abl‑specific antisera to probe the fusion protein. The experiments confirmed that P210 is produced from the 8.5‑kb transcript and identified a 190‑kDa phosphoprotein that may represent the normal bcr protein in HeLa and K562 cells.

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.