title: Detection and monitoring of trisomy 8 by fluorescence in situ hybridization in acute myeloid leukemia: a multicentric study.
abstract: OBJECTIVE
  The role of fluorescence in situ hybridization (FISH) in the detection and monitoring of trisomy 8 (+8) in acute myelogenous leukemia (AML) has not been defined exactly. This multicentric study was performed in order to: i) analyze the sensitivity of interphase FISH with respect to conventional chromosome analysis (CCA) in detecting +8; ii) compare the results of FISH and CCA in the quantitation of the frequency of +8-positive cells; iii) analyze the possible role of FISH in the cytogenetic follow-up of patients with +8.
  
  
  METHODS
  One hundred and ninety-eight nonconsecutive patients with a diagnosis of AML seen at five centers over a 3-year period were studied by CCA and FISH with a chromosome 8-specific centromeric probe. Two hundred interphase cells were scored in each test and the cut-off for the recognition of +8 was set at 3%. An irrelevant pericentromeric probe was used as negative control in those cases with an apparently normal karyotype and trisomy 8 in interphase cells. FISH studies were conducted 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 metaphases with +8, 2.3% interphase cells with 3 signals were seen. Fourteen additional cases with occult +8 were detected by FISH, which showed 4-22% interphase cells with three signals; 6 patients had an abnormal karyotype without +8, 3 had a normal karyotype, 5 had no analyzable mitoses. In 24 cases with > 15 analyzable metaphases, percent variations between CCA and FISH in the estimation of the size of the trisomic clone 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 at 20-32 months.
  
  
  CONCLUSIONS
  It is concluded that FISH was a valuable method in this multicentric study since it showed greater sensitivity than CCA in detecting minor clones with +8, in patients with both normal and abnormal karyotypes. The role of FISH in the cytogenetic follow-up of trisomies in AML patients may be promising.
authors.affiliation: Institute of Hematology, University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.forename: R
authors.initials: R
authors.lastname: Bigoni
authors.forename: M G
authors.initials: MG
authors.lastname: Roberti
authors.forename: A
authors.initials: A
authors.lastname: Bardi
authors.forename: G M
authors.initials: GM
authors.lastname: Rigolin
authors.forename: N
authors.initials: N
authors.lastname: Piva
authors.forename: M
authors.initials: M
authors.lastname: Mancini
authors.forename: M
authors.initials: M
authors.lastname: Nanni
authors.forename: G
authors.initials: G
authors.lastname: Alimena
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
authors.forename: C
authors.initials: C
authors.lastname: Matteucci
authors.forename: R
authors.initials: R
authors.lastname: La Starza
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
authors.forename: P
authors.initials: P
authors.lastname: Cavigliano
authors.forename: E
authors.initials: E
authors.lastname: Genini
authors.forename: A
authors.initials: A
authors.lastname: Zaccaria
authors.forename: N
authors.initials: N
authors.lastname: Testoni
authors.forename: C
authors.initials: C
authors.lastname: Carboni
authors.forename: G
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D014314:Trisomy / Q000175:diagnosis*