VALUE OF FLUORESCENCE IN-SITU HYBRIDIZATION FOR DETECTING THE BCR ABLGENE FUSION IN INTERPHASE CELLS OF ROUTINE BONE-MARROW SPECIMENS/

Fluorescence in situ hybridization (FISH) is a new technique that allo ws demonstrating of the bcr/abl gene fusion in bone marrow cells of pa tients with Philadelphia translocation (Ph)positive chronic myeloid le ukemia (CML). In this study, bone marrow samples of 150 patients were investigated routinely by interphase FISH, cytogenetics, and bone marr ow histopathology. In 20 patients with reactive hyperplasia of the gra nulopoiesis and normal karyotypes, FISH revealed nonspecific bcr/abl f usion signals at a mean frequency of 2.7% of the cells examined. The c utoff level for specific fusion signals was set at three times the sta ndard deviation (9.0%). None of the 29 cytogenetically Ph-negative pat ients with myeloproliferative disease other than CML had fusion signal s exceeding 9%. The mean frequency of specific fusion signals in nontr eated patients with CML (n = 59) was 92.7%, and 49.3% in patients with Chit who received therapy (n = 42). For diagnosing Ph-positive CML, i nterphase FISH has been faster, more reliable, and more sensitive than cytogenetics, which was successful in 54 of 59 patients investigated at first diagnosis but only in 27 of 42 patients receiving therapy, an d it failed to detect Ph-positive cells in three patients with CML. Ho wever, small percentages of less than 9.0% of cells with bcr/abl fusio n signals were below the threshold of interphase FISH, thereby limitin g its use for detecting minimal residual disease.