The incidence, type, and subsequent evolution of 14 variant Ph1 translocations in 180 South African patients with Ph1-positive chronic myeloid leukemia.

A Philadelphia (Ph1) chromosome translocation was found in 180 of 198 cases of chronic myeloid leukemia (CML). A standard t(9;22) was present in 166 patients, 83 of whom were black, 79 white, and 4 of "mixed" ancestry; whereas a variant Ph1 translocation was detected in 14 patients (7.8%), 11 of whom were black and only 3 white. There was a higher frequency of a variant Ph1 among black patients compared with whites. The significantly higher frequency of a variant among our patients compared with surveys from elsewhere could be due to differing environmental agents. Simple variants were detected in four patients. Complex variants were found in eight cases; in one of these patients, only chromosomes #9 and #22 were involved, but a complex rearrangement of chromosome #9 had occurred. A "masked" Ph1 translocation was detected in two cases, both of which showed monosomy #22 because the Ph1 chromosome was incorporated or interchanged with chromosome #9. Karyotypic evolution of the Ph1-positive cell line was observed more frequently in the variant group (71.4%) than the standard group (29.5%). This difference was significant (p less than 0.005). There was no difference in the type of clonal changes seen in standard and variant groups. The majority of clonal changes were observed during the acute stage in both groups. In the variant group, there was no obvious correlation between the type of variant, type of clonal change, blast morphology, or survival. Their initial survival pattern resembled that of Ph1-negative cases, but those patients who survived longer than 1 year showed a survival trend similar to standard Ph1-positive cases. Possible explanations for the specificity of chromosome #22 involvement and the constancy of the 22q11 breakpoint in all these variant translocations are discussed.