DETECTION AND MONITORING OF TRISOMY-8 BY FLUORESCENCE IN-SITU HYBRIDIZATION IN ACUTE MYELOID-LEUKEMIA - A MULTICENTRIC STUDY

Background and Objective. The role of fluorescence in situ hybridizati on (FISH) in the detection and monitoring of trisomy 8 (+8) in acute m yelogenous leukemia (AML) has not been defined exactly. This multicent ric study was performed in order to: i) analyze the sensitivity of int erphase FISH with respect to conventional chromosome analysis (CCA) in detecting +8; ii) compare the results of FISH and CCA in the quantita tion of the frequency of +8-positive cells; iii) analyze the possible role of FISH In the cytogenetic follow-up of patients with +8. Design and Methods. One hundred and ninety-eight nonconsecutive patients with a diagnosis of AML seen at five centers over a 3-year period were stu died by OCA and FISH with a chromosome 8-specific centromeric probe. T wo hundred interphase cells were scored in each test and the cutoff fo r the recognition of +8 was set at 3%. An irrelevant pericentromeric p robe was used as negative control in those cases with an apparently no rmal karyotype and trisomy 8 in interphase cells. FISH studies were co nducted at diagnosis and, in 14 cases with +8, on 1.5 occasions during follow-up. Results. Karyotype aberrations were seen in 121 cases (61. 1%), with +8 being present in 38 of them (16 as the sole aberration). Interphase FISH detected +8 in 37/38 cases; in a patient with 1/10 met aphases with +8, 2.3% interphase cells with 3 signals were seen. Fourt een additional cases with occult +8 were detected by FISH, which showe d 4-22% interphase cells with three signals; 6 patients had an abnorma l karyotype without +8, 3 had a normal karyotype, 5 had no analyzable mitoses. In 24 cases with >15 analyzable metaphases, percent variation s between CCA and FISH in the estimation of the size of the trisomic c lone ranged between 0.4% and 51%, median value 22%. Underestimation of the percent of trisomy 8 by FISH occurred in all 10 cases with >90% 8 metaphases. In 7/14 cases investigated sequentially, FISH detected 5 -35% trisomic cells in the BM after induction therapy (4 CR, 3 PR); 4 cases relapsed with +8 at 8-15 months. The absence of +8 in remission marrows was documented in the remaining 7 cases, 4 of which relapsed a t 20-32 months. Interpretation and Conclusions. It is concluded that F ISH was a valuable method in this multicentric study since it showed g reater sensitivity than CCA in detecting minor clones with +8, in pati ents with both normal and abnormal karyotypes. The role of FISH in the cytogenetic follow-up of trisomies in AML patients may be promising. (C) 1998, Ferrata Storti Foundation.