Small Percent of Additional Abnormal Clones to Ph Chromosome in the Early Chronic Phase Detected by Large Number of Karyotype Analysis and Transformation to Blastic Crisis in Chronic Myelocytic Leukemia

Extensive study on Chronic Myelocytic Leukemia (CML) was performed sequentially from the time of early chronic phase to the blastic crisis (BC) phase. A large number of 80-385 metaphases were karyotyped at the time of diagnosis in 16 patients and 13 in BC phase. Three patients were BC phase at diagnosis. All the patients had small percent of clones with additional chromosome aberration in 1.3-12.4% of the observed cells in the early stages of chronic phase. The additional abnormal clones which had existed at the time of diagnosis of early chronic phase remarkably increased in the BC phase of only 5 of 10 patients examined, because 3 of the 13 patients had no additional chromosome aberrations in BC phase. New abnormal clones which were not detected at the time of diagnosis emerged into the BC phase of 5 of the 10 patients. These additional clones were not always associated with the development of the BC. In all 3 patients diagnosed at 10.6 months before developing BC, small sized clone found in early chronic phase related to main clone in BC. Then, detection of additional clones in chronic phase for early detection of BC clone can be useful at only 10.6 months before BC. However, weak correlation between frequency of additional aberrations with Ph chromosome and duration of chronic phase was found. These findings also suggested that leukemic cells harboring Ph chromosome are high chromosome instability, in which are intrinsically labile for the acquisition of various additional chromosome aberrations at any stage, which might be related with resistance to chemotherapy, and therapies of interferon α and imatinib.