Correlation of M-bcr breakpoint with different chromosomal abnormalities in blast crisis Ph1-positive CML

The molecular genetics of the Philadelphia (Ph1) chromosome, arising from a reciprocal translocation between chromosomes 9 and 22 and involving the genes abl and bcr, has been well characterized. However, the Ph1 chromosome is usually the sole cytogenetic abnormality during the chronic phase of the disease with additional karyotypic abnormalities arising prior to, or during the onset of the blast or acute phase. We have shown that patients with a breakpoint within the 5' region of the M-bcr of the bcr gene have a different sub-set of chromosomal bands involved in the cytogenetic abnormalities observed during the development of blast crisis than those patients with a 3' breakpoint. This suggests that different mechanisms of progression to blast crisis may be implicated for the subgroups groups of patients.