Acute promyelocytic leukaemia (APL) is characterized by the t(15;17)(q22;q21) leading to the formation of
PML-RARalpha and RARalpha-PML fusion genes which provide suitable targets for the assessment of
minimal residual disease (MRD). Studies have focused upon detection of
PML-RARalpha because, although assays for RARalpha-PML transcripts are more sensitive, they are not applicable to 25% of cases. Among patients receiving standard
therapy (ATRA and
anthracycline-based
chemotherapy), qualitative assays using a nested
reverse transcriptase-polymerase chain reaction (RT-PCR), which typically achieve sensitivities of 1 in 10(4), have been found to provide independent prognostic information suitable for directing an approach to treatment. Detection of
PML-RARalpha at the end of consolidation, or subsequent recurrence of PCR positivity, heralds relapse, which may, however, be averted by additional
therapy leading to improvements in survival for this "high-risk" subgroup of patients. MRD analysis has also proved of value in predicting response to autologous transplant procedures undertaken in second complete remission and in directing the need for additional
therapy in the post-
transplantation setting. Overall, these studies undertaken within the context of a relatively homogeneous disease entity confirm that MRD monitoring provides independent prognostic information, serving as a valuable model for improving treatment strategy in other molecularly defined subsets of acute myeloid leukaemia (AML). Nevertheless, conventional nested RT-PCR assays fail to detect residual disease in a significant proportion of patients who ultimately relapse, which may be a reflection of
RNA quality and/or assay sensitivity. Therefore, it is hoped that "real-time" quantitative RT-PCR technology (RQ-PCR) which permits quantification of fusion gene transcripts in relation to endogenous control genes will be even more predictive of outcome and achieve greater standardization of MRD detection in the context of large-scale clinical trials.