Introduction: Chronic myeloid leukaemia (CML) is characterised by the formation of the BCR/ABL fusion gene, usually as a result of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Materials and Methods: The incidence of both typical and atypical BCR/ ABL gene rearrangements was determined in 110 patients suspected of CML using dual fusion fluorescence in situ hybridisation (DF-FISH) probes. Results: Eighty-seven per cent of CML patients showed Ph translocation while 13% were negative for the Ph chromosome. About 71.9% of Ph-positive patients displayed the typical DF-FISH signal pattern. Atypical patterns among the Ph-positive patients included the concurrent loss of residual proximal 9q and distal 22q (10.4%), complex translocation with additional partners (9.4%), supernumerary Ph (3.1%), loss of residual 9q sequences proximal to breakpoint (3.1%), and deletion of distal derivative 22q signal (2.1%). Cryptic genetic alterations with loss of proximal 9q sequences were found in 13.5% of CML Ph-positive patients, which is associated with poor prognosis. Fusion signals were detected in 57.1% of CML Ph-negative patients, indicating cryptic BCR/ABL rearrangements (i.e., masked Ph). Conclusion: FISH is able to detect BCR/ABL fusion in CML with masked or variant Ph not apparent with conventional karyotyping. Establishment of signal patterns with FISH is important as atypical patterns may have clinical prognostic implications.
Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder of the haematopoietic stem cells. About 90% to 95% are characterised cytogenetically by the presence of the Philadelphia (Ph) chromosome, due to a translocation between chromosomes 9 and 22. This rearrangement results in the formation of a chimeric BCR/ ABL fusion gene on the derivative chromosome 22.1 The fusion gene is transcribed and spliced into a 8.5 kb chimeric messenger RNA with b2a2 and b3a2 configurations.2 The translation product is a 210 kD BCR/ABL protein that contributes to CML pathogenesis.
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