title: Molecular cytogenetic characterization of Philadelphia-negative rearrangements in chronic myeloid leukemia patients.
abstract: BACKGROUND
  The BCR/ABL gene rearrangement is generated by a reciprocal translocation t(9;22)(q34;q11) in chronic myeloid leukemia (CML) patients. In most cases, it is cytogenetically visualized by the Philadelphia (Ph) chromosome. About 5-10% of CML patients lack cytogenetic evidence of the Ph translocation but show BCR/ABL fusion by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR). Deletions around the breakpoints on derivative chromosome 9 including 5'ABL and 3'BCR sequences occur in 10-15% of Ph-positive CML patients and are thought to have prognostic significance.
  
  
  METHODS
  We explored cryptic rearrangements involving chromosomes 9 and 22 in 3 CML patients with an apparently normal bone marrow karyotypes using multiplex RT-PCR and FISH with commercial and home-brew probes.
  
  
  RESULTS
  The BCR/ABL fusion transcripts were detected by RT-PCR. Using commercial FISH probes, the BCR/ABL fusion gene was found on chromosome 22 in two patients and on chromosome 9 in one patient. Consecutive FISH assays clarified the mechanism of the masked Ph chromosome: in the 3 patients, Ph rearrangement resulted from double mechanism consisting in standard translocation t(9;22)(q34;q11) followed by a second reversed translocation t(9;22)(q34;q11). One patient achieved major cytogenetic response after 6 months of imatinib therapy, and one patient had successful bone marrow transplant.
  
  
  CONCLUSIONS
  In this study, we have characterized three Ph-negative CML patients with cryptic BCR/ABL rearrangement generated after an uncommon mechanism involving two sequential translocations and confirm that the BCR/ABL hybrid gene may be located on other sites than 22q11. Ph-negative CML patients with BCR/ABL fusion gene have the same prognosis as patients with classical t(9;22).
authors: Department of Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia. aydabennour@yahoo.fr
authors: Ayda
authors: A
authors: Bennour
authors: Hatem
authors: H
authors: Bellâaj
authors: Yosra
authors: Y
authors: Ben Youssef
authors: Moez
authors: M
authors: Elloumi
authors: Abderrahim
authors: A
authors: Khelif
authors: Ali
authors: A
authors: Saad
authors: Halima
authors: H
authors: Sennana
mesh_terms: D000293:Adolescent; D000328:Adult; D002871:Chromosome Banding; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015331:Cohort Studies; D003582:Cytogenetics / Q000379:methods; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D014178:Translocation, Genetic