INTERPHASE CYTOGENETICS AND COMPETITIVE RT-PCR FOR RESIDUAL DISEASE MONITORING IN PATIENTS WITH CHRONIC MYELOID-LEUKEMIA DURING INTERFERON-ALPHA THERAPY

There is a need for fast and sensitive methods to evaluate the respons e of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphi a (Ph) chromosome-positive metaphases. We have used interphase FISH (f luorescence in situ hybridization) and competitive RT-PCR (reverse tra nscriptase-polymerase chain reaction) techniques for detection of BCR- ABL-positive cells to measure suppression of leukaemic clone in a seri es of 51 follow-up samples from 24 CML patients undergoing IFN-alpha t reatment. Interphase FISH analysis of the malignant clone in bone marr ow using BCR and ABL probes was found to be highly correlated to conve ntional G-banding metaphase examination (r = 0.98). RT-PCR quantificat ion of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concl uded that interphase FISH and competitive RT-PCR provide reliable info rmation on residual tumour burden and response to IFN-alpha in CML pat ients. These molecular methods may significantly improve the efficienc y of residual disease monitoring during IFN-alpha therapy of CML.