FISH versus real-time quantitative PCR for monitoring of minimal residual disease in chronic myeloid leukaemia patients on tyrosine kinase inhibitor therapy

INTRODUCTION: BCR-ABL fusion gene, the oncogenic driver of CML, results from a translocation between short arms of chromosome 9 and 22. Monitoring of CML patients during treatment is essential, not only for tailoring the treatment but also to detect early relapse to enable timely intervention. Commonly used methods for detection of residual disease are conventional karyotyping, FISH and molecular methods. In this study, we compared FISH with QRT-PCR for detection of residual disease in CML.

MATERIALS AND METHODS: CML patients on tyrosine kinase inhibitor (TKI) therapy and on regular follow up at University Kebangsaan Malaysia Medical Center (UKMMC) were selected. A comparative study was conducted between FISH and QRT-PCR for BCR-ABL transcripts at diagnosis and during follow-up.

RESULTS: There was good correlation between FISH and QRT-PCR for BCR-ABL. At 6th month of follow-up post diagnosis, FISH had a sensitivity of 83.3% and specificity of 65.2% (k >0.339, p<0.033). At 12th month, the sensitivity of FISH was 83% and the specificity was 59.1% (k >0.286, p <0.065). Similarly, at the 24th month, FISH had a sensitivity of 100% and specificity of 68.8% (k >0.642, p<0.000).

DISCUSSION: Early achievement of major molecular response (MMR) and complete cytogenetic remission (CCyR) were reliable predictors of long-term maintenance of molecular remission.