Combined cytogenetic, FISH and molecular analysis in acute promyelocytic leukaemia at diagnosis and in complete remission.
This study reports the results of a simultaneous application of cytogenetic fluorescence in situ hybridization (FISH) and molecular analysis (RT-PCR) in 28 APL cases (23 M3 and five M3v; 26 studied at diagnosis and two at relapse). FISH on metaphases identified the t(15;17) in all 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 evaluate residual disease; the duration of CR at the time of analysis ranged between 1 and 16 months, with three patients being studied twice. Comparison of RT-PCR and FISH results showed a very good correlation. In fact, of the 10 samples which were RT-PCR positive for residual disease, all were also recognized by interphase FISH, and eight were positive by metaphase FISH. Of the three samples negative at RT-PCR, all were also negative at the interphase FISH. The results of this study indicate that: (a) the t(15;17) is present in all cases positive for the PML/RAR alpha rearrangement, thus in virtually all true APLs; (b) standard cytogenetics, capable of unravelling the t(15;17) in only 68% of cases, enables recognition of additional chromosome changes of potential clinical and prognostic significance; (c) FISH on interphase nuclei is a reliable tool for the monitoring of residual disease, with a sensitivity greater than that of FISH on metaphase cells and superimposable to that of RT-PCR.
Department of Human Biopathology, University of Rome La Sapienza, Italy.
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D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic
D005819:Genetic Markers