Utility of molecular genetic analysis of bcr rearrangement in the diagnosis of chronic myeloid leukemia.

Two DNA probes for the breakpoint cluster region (bcr) of chromosome # 22 have been used to determine the proportion of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) cases that can be diagnosed by Southern blot analysis. Studies on 17 normal individuals and 17 patients with lymphomas and leukemias (other than CML) indicated that for the restriction enzymes chosen, only expected germ line DNA bands were obtained. In contrast, novel DNA bands interpreted as being the product of translocation within the bcr region could be demonstrated in 31 of 31 cases of Ph-positive CML. One commercially available 1.2 kb bcr probe detected most cases of CML. Because of the frequent presence of deletion of part of the bcr region, however, a probe from the 5' end of bcr is essential to detect some cases. An analysis of the bcr breakpoints occurring in CML patients suggested a difference in the location of the breakpoints for the blast crisis patients versus chronic phase patients although the difference between these two groups was not statistically significant. It is concluded that bcr analysis provides a powerful aid in the diagnosis of CML. This technique is of particular merit in cases when cytogenetic analysis is inconclusive and has considerable potential for improved speed and sensitivity of diagnosis.