A dual colour dual fusion fluorescence in situ hybridisation study on the genesis of complex variant translocations in chronic myelogenous leukaemia

Complex variant 9;22 translocations occur in a significant minority of chronic myelogenous leukaemia (CML) patients. Different mechanisms of their formation have been described. We report dual colour dual fusion fluorescence in situ hybridisation data in 12 Chinese CML patients with complex translocations. Three previously reported breakpoint hotspots in a third partner chromosome (14q32, 17q25, 1q2l) were observed. In 10/12 (83.3%) patients, the abnormality occurred as a single step 3-break event. Only a single abnormal clone harbouring the complex translocation was seen in this group. The remaining 2 cases in the chronic phase showed a 4-break mechanism (2/12,16.7%). Deletion of 5' ABL at der(9) was not observed in any of the 12 patients, however, the loss of 3' BCR was observed in 1 patient (1/12, 8.3%). Together with previous findings, these data suggest that these variant translocations occur more often as a 3-break single-step process with no reciprocal ABL-BCR fusion. On the other hand, a 4-break event is also regularly seen during the initial stages of leukaemogenesis, which likely predisposes to der(9) deletion. The observed difference in rates of der(9) deletion reported in a series of CML patients with variant translocations may be related to a difference in rates of a 4-break event.published_or_final_versio