With the development of fluorescencein situhybridization (FISH), it was possible to detect theBCR-ABLfusion signal in both metaphase spreads and interphase cells of patients with chronic myeloid leukemia (CML). However, the use of FISH to detect residual disease in patients with CML post therapy was limited by the false positive rate using the early single fusion probes. Therefore, dual fusion probes that created a fusion signal on the derivative chromosome 9 in addition to the fusion sifnal on the Philadelphia chromosome or derivative chromo-some 22 were developed. Using these second-generation probes, it was discovered that a significant proportion of CML cases has a sub-microscopic deletion at the site of theABL-BCRfusion. This chapter outlines a testing strategy to identify deleltions of the derivative chromo-some 9 and to use combinations of probes to identify residual disease in these cases.
