Detection of rearrangement within the breakpoint cluster region of chromosome 22 in the diagnosis of chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is characterised by the presence of a Philadelphia (Ph) chromosome in approximately 95% of patients. Molecular analysis has shown that the Ph chromosome translocation breakpoints are clustered within 5.8 kb on chromosome 22 (breakpoint cluster region or bcr). This has facilitated the diagnosis of CML by nucleic acid hybridisation using probes specific for the bcr to detect DNA rearrangement in this region. Forty patients diagnosed with CML, including four with variant Ph chromosome translocations and three with normal karyotypes were analysed for rearrangement within the bcr. All except one patient with Ph negative CML had rearrangement within the bcr. In contrast, none of the patients diagnosed with other hematological disorders such as the myelodysplastic or myeloproliferative syndromes (16 patients), acute myeloid leukemia (AML) (six patients), acute lymphoblastic leukemia (ALL) (five patients), including Ph positive ALL (two patients), showed rearrangement within the bcr. Analysis for rearrangement within the bcr is useful in the diagnosis of CML, especially when cytogenetic analysis is unsuccessful or in patients with normal karyotypes or variant Ph chromosome translocations.