The bcr gene is joined to c-abl in Ph1 chromosome negative chronic myelogenous leukemia

The relationship between chronic myelogenous leukemia (CML) with and without the Ph1 chromosome is controversial. Although some suggest that these disorders are identical, other reports suggest that Ph1 chromosome negative CML is a distinct entity. To resolve this issue, we studied 11 patients with Ph1 chromosome negative CML for the translocation of the Abelson proto-oncogene (c-abl) to the breakpoint cluster region gene (bcr), internal genomic rearrangement of bcr, and transcription of a chimeric bcr/abl mRNA. Our data indicate that c-abl is translocated to chromosome 22 where it is inserted after exon "2" or "3" of the bcr gene. This results in transcription of a chimeric bcr/abl mRNA in which the splice is between bcr exon "2" or "3" and c-abl exon 2. These data suggest that CML with and without the Ph1 chromosome are molecularly identical disorders with regard to bcr and abl.