Cytogenetics of chronic myelogenous leukaemia

The Philadelphia (Ph) chromosome is present in the leukaemic cells of most patients with chronic myelogenous leukaemia. Variant translocations occur in 10% of patients but breakpoints on chromosomes 9 and 22 remain the same, so prognosis of these patients is unchanged. Clonal evolution is infrequent in chronic phase and its significance depends on the specific chromosome involved, the number of metaphases affected and the timing in the chronic phase. The majority of patients in blastic phase demonstrate clonal evolution; three specific abnormalities (+Ph, +8 and isochromosome 17q) are present in 70% of patients. Loss of the Ph chromosome on therapy is associated with prolonged survival. For monitoring these events conventional G-band cytogenetics (CG) is essential at presentation to characterize the disease cytogenetically, while fluorescence in situ hybridization (FISH) on hypermetaphase preparations (hypermetaphase FISH (HMF)) is important for establishing the specific frequency of Ph⁺ cells. During treatment FISH on interphase cells (I-FISH) can monitor the level of Ph⁺ cells in circulation, while CG may be used to identify any suspected clonal evolution. Where I-FISH is negative, HMF is essential to evaluate minimal residual disease.