title: Rapid diagnostic approach to PML-RARalpha-positive acute promyelocytic leukemia.
abstract: BACKGROUND
  Acute promyelocytic leukemia (APL) is a distinct entity characterized by a specific bone marrow morphology and a rearrangement of the PML- and the RARalpha-gene mostly due to a balanced translocation between the long arm of chromosome 15 with a breakpoint in 15q22 and the long arm of chromosome 17 with a breakpoint in 17q12-21. The introduction of all trans retinoic acid (ATRA) into treatment protocols has improved the outcome of APL dramatically. Therefore, it is essential to establish the diagnosis of APL as quickly and as reliably as possible.
  
  
  METHODS
  We investigated 1714 newly diagnosed AML. In 92 cases an AML M3 (n=67) or M3v (n=25) was diagnosed using cytomorphology. In all these cases chromosome banding analysis and molecular studies were performed.
  
  
  RESULTS
  In 3/92 APL cases (3.2%) normal chromosomes 15 and 17 in chromosome banding analysis were observed. In these cases either an insertion of parts of the PML-gene into the RARalpha-locus or an insertion of parts of the RARalpha-gene into the PML-locus was detected by FISH analysis. In all three patients a PML-RARalpha-rearrangement was also observed by RT-PCR.
  
  
  CONCLUSIONS
  A small subgroup of APL shows cryptic rearrangements of the PML- and RARalpha-gene that are undetectable by cytogenetics. This is analogous to Ph-negative, BCR-ABL-positive CML cases. FISH and RT-PCR have to be performed in all cases that show the typical characteristics of AML M3 or M3v in cytomorphology in addition to chromosome banding analysis.
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany. claudia.schoch@med3.med.uni-muenchen.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Schoch
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Eva
authors.initials: E
authors.lastname: Lengfelder
authors.forename: Helmut
authors.initials: H
authors.lastname: Löffler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002871:Chromosome Banding; D020732:Cytogenetic Analysis / Q000379:methods; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein