DIAGNOSIS AND MONITORING OF CHROMOSOME-ABERRATIONS IN HEMATOLOGICAL MALIGNANCIES BY FLUORESCENCE IN-SITU HYBRIDIZATION

Besides its application in biological research, fluorescence in situ h ybridization (FISH) is increasingly used for the cytogenetic analysis of human malignancies. Compared to conventional cytogenetic analysis, FISH allows delineation of specific numerical and structural chromosom e aberrations in interphase cells (interphase cytogenetics), We have d eveloped sets of genomic DNA probes for the identification of chromoso me aberrations associated with chronic lymphocytic leukemia (CLL), chr onic myeloid leukemias (CML), and acute myeloid leukemia (AML). In CLL , interphase cytogenetics will greatly contribute to the evaluation of the true incidence of specific chromosome aberrations and will provid e the basis for more accurate correlations with the clinical outcome, The Philadelphia chromosome can be detected by FISH with high specific ity and sensitivity in both CML and acute lymphoblastic leukemia, In C ML, it can be used to better assess the cytogenetic remission status f ollowing therapy with interferon-alpha, Finally, in AML interphase cyt ogenetics provides a rapid and reliable technique for the identificati on of chromosome aberrations which are one of the most important progn ostic factors in this disease. With the design of complex DNA probe se ts and the development of digital microscopy and automated image analy sis, it will be possible to use such disease-specific probe sets for m onitoring residual disease following chemotherapy.