Philadelphia-positive chronic myelogenous leukemia with breakpoint 5' of the breakpoint cluster region but within the bcr gene.

We report on the first Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) characterized by a rearrangement within the 5' part of the bcr gene on chromosome 22, but outside the restricted breakpoint cluster region. In situ hybridization studies revealed a translocation of the c-abl oncogene to the Ph chromosome and Northern blot analysis identified a chimeric 8 kb bcr/abl RNA transcript in leukemic cells. These data suggest that 1. less bcr coding sequences than previously assumed may be essential for the putative transforming activity of the rearranged bcr/abl gene and 2. the bcr probes currently used for diagnostic purposes could miss Ph-positive CML cases.