Monitoring minimal residual disease in AML: the right time for real time

Detection of minimal residual disease (MRD) by polymerase chain reaction (PCR) has become an essential tool for molecular monitoring of acute myeloid leukemia (AML). Currently, specific translocation markers are available for 40-50% of AMLs. Expression markers may widen this spectrum to 70-90%. Quantitative PCR (Q-PCR, real-time PCR) is now as sensitive as conventional two-step PCR and could improve as well as facilitate clinical decision-making. Q-PCR has been applied to a variety of molecular markers, delineating threshold levels early after induction therapy, for postinduction monitoring, as well as for the detection of relapse. For most markers, lack of decline of transcript levels by less than 2 logs after chemotherapy has been established as a poor prognostic sign. Moreover, increases in transcript levels are almost invariably associated with relapse. However, the predictive value of PCR negativity after chemotherapy is not as clear. The major tasks for the future will be standardization of Q-PCR techniques, exact definition of threshold levels, and monitoring schedules in bone marrow (BM) and peripheral blood (PB), as well as investigation of novel markers found by microarray analysis.