Complex chromosome rearrangements may locate the bcr/abl fusion gene sitesother than 22q11

Background and Objectives. From 58% of Philadelphia (Ph) positive patients with chronic myeloid leukemia (CML) show variant translocations in which at least a third chromosome in addition to 9q34 and 22q11 is involved. The fo rmation mechanisms and clinical significance of variant Ph translocations a re still unclear. The BCR/ABL chimeric gene encoding for chimeric proteins is always present and maps on the 22q- regardless of the type of translocat ion. We studied two apparently Ph negative CML patients with unusual karyot ypes both showing a typical b3a2 rearrangement. Design and Methods. Dual-color fluorescence in situ hybridization (FISH) ca n visualize BCR and ABL genes and localize the BCR/ABL fusion gene. We used FISH to study the formation mechanisms of variant Ph translocations in two patients. Results. The chimeric BCR/ABL gene was located on a locus other than the ex pected 22q11 in both patients. In the first case the fusion signal was pres ent on the 9q34 band whereas in the second patient it was detected on chrom osome 8, involved in masked Ph formation. Interpretation and Conclusions. The location of the hybrid BCR/ABL gene on chromosomes other than 22q is a rare event which can only be observed using the FISH technique. When these unusual translocations occur the hypothesis most often put forward is that several consecutive cytogenetic events have taken place. The factors which regulate the formation Of these breakpoints have yet to be clarified. The FISH technique allows the identification of chromosome rearrangements that could not otherwise be detected by conventio nal banding procedures. The location of the hybrid BCR/ABL gene on sites ot her than 22q11 represents a rare type of variant Ph translocation. The real frequency and clinical significance of such rearrangements need to be inve stigated. (C) 2000, Ferrata Storti Foundation.