COMBINED CYTOGENETIC, FISH AND MOLECULAR ANALYSIS IN ACUTE PROMYELOCYTIC LEUKEMIA AT DIAGNOSIS AND IN COMPLETE REMISSION

This study reports the results of a simultaneous application of cytoge netic fluorescence in situ hybridization (FISH) and molecular analysis (RT-PCR) in 28 APL cases (23 M3 and live M3v; 26 studied at diagnosis and two at relapse). FISH on metaphases identified the t(15;17) in al l cases who were positive for the PML/RAR alpha transcript by RT-PCR, Conventional cytogenetics revealed the t(15;17) in only 68% of cases. However, it enabled the detection of additional chromosome changes in five cases, three of whom were M3v. 11 patients were also investigated during complete remission (CR) by both FISH and RT-PCR, in order to e valuate residual disease; the duration of CR at the time of analysis r anged between 1 and 16 months, with three patients being studied twice . Comparison of RT-PCR and FISH result showed a very good correlation, In fact, of the 10 samples which were RT-PCR positive for residual di sease, all were also recognized by interphase FISH, and eight were pos itive by metaphase FISH, Of the three samples negative at RT-PCR, all were also negative at the interphase FISH, The results of this study i ndicate that: (a) the t(15;17) is present in all cases positive for th e PML/RAR alpha rearrangement, thus in virtually all true APLs; (b) st andard cytogenetics, capable of unravelling the t(15;17) in only 68% o f cases, enables recognition of additional chromosome changes of poten tial clinical and prognostic significance; (c) FISH on interphase nucl ei is a reliable tool for the monitoring of residual disease, with a s ensitivity greater than that of FISH on metaphase cells and superimpos able to that of RT-PCR.