title: Correlation of cytogenetics, BCR-ABL PCR studies and fluorescence in situ hybridisation (FISH) in adult acute lymphoblastic leukaemia.
abstract: BACKGROUND
  Philadelphia positive (Ph+) acute lymphoblastic leukaemia (ALL) accounts for 11-29% of adult ALL. Reverse transcriptase polymerase chain reaction (RT-PCR) for the BCR-ABL fusion mRNA has identified patients with the fusion mRNA without cytogenetic evidence of the 9;22 translocation. The reason for discrepancies between cytogenetic and molecular diagnoses is unclear.
  
  
  OBJECTIVE
  Our aim was to study cases of ALL with discordant cytogenetic and RT-PCR results and identify any reasons for such discrepancies.
  
  
  METHODS
  Laboratory records were scanned for cases of ALL tested by both RT-PCR and cytogenetics and positive by either for the 9;22 translocation. Fluorescence in situ hybridisation (FISH) was used to study discordant results where a specimen was available.
  
  
  RESULTS
  We identified 15 patients with ALL who had both cytogenetic and RT-PCR studies for BCR-ABL. Seven had discordant results; five patients had positive RT-PCR studies with normal (four/five) or abnormal but Ph negative cytogenetics (one/five), and two were Ph+ but RT-PCR negative. FISH, using Vysis LSI bcr/abl translocation probes, showed fused signals in 12% interphase cells but not in metaphase cells in one specimen with normal cytogenetics, and 6% interphase cells in the Ph negative patient with abnormal cytogenetics. This second patient subsequently relapsed with a minor Ph+ cell line derived from the Ph negative line.
  
  
  CONCLUSIONS
  These results confirmed the need for both cytogenetics and RT-PCR to identify Ph+ ALL. FISH did not show sub-microscopic rearrangements of BCR-ABL in normal metaphases. Failure to identify the Philadelphia chromosome cytogenetically appeared due rather to Ph+ cells failing to divide.
authors.affiliation: Victorian Cancer Cytogenetics Service, St Vincent's Hospital, Melbourne, Vic. campbelj@svhm.org.au
authors.forename: L J
authors.initials: LJ
authors.lastname: Campbell
authors.forename: A
authors.initials: A
authors.lastname: Martinow
authors.forename: P M
authors.initials: PM
authors.lastname: Michael
authors.forename: J S
authors.initials: JS
authors.lastname: White
authors.forename: K C
authors.initials: KC
authors.lastname: Rayeroux
authors.forename: E H
authors.initials: EH
authors.lastname: Januszewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016044:Fusion Proteins, bcr-abl