Breakpoints on chromosomes 9 and 22 in Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Amplification of rearranged c-abl oncogenes in CML blast crisis.

We surveyed 20 Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) samples by Southern blot hybridization to determine the location of the breakpoints that occur on chromosomes 9 and 22 in the Ph1 translocation. Only 3 of 20 samples exhibited breakpoints on chromosome 9 within 18 kilobases (kb) of the v-abl homologous sequences. Mapping of these three chromosome 9 breakpoints indicates that each is at a separate location within this 18-kb region, indicating that there are no breakpoint "hot spots" in this area. In contrast, all 20 CML samples exhibited breaks on chromosome 22 within a 5.0-kb Bgl II fragment that lies within the previously described breakpoint cluster region (bcr). Several patients with CML blast crisis exhibiting multiple Ph1 chromosomes/metaphase exhibited amplified and rearranged c-abl-related fragments. These additional Ph1 chromosomes in blast crisis cells do not arise from a second, independent 9:22 translocation but rather result from a duplication of the preexisting Ph1 chromosome.