DETECTION OF MINIMAL RESIDUAL DISEASE IN ACUTE-LEUKEMIA PATIENTS

Diagnostic techniques, routinely used in clinical practice for monitor ing acute leukemia patients, are able to detect only 1-5% of malignant cells. At present, two main techniques are being introduced for detec tion of minimal residual disease (MRD) in leukemia, namely immunologic al marker analysis and the polymerase chain reaction (PCR) technique w ith general sensitivity of 10(-4)-10(-5). Immunological marker analysi s allows detection of unusual and aberrant immunophenotypes, and is us ually performed by flow cytometry. PCR analysis allows detection of le ukemia-specific DNA sequences, such as fusion regions of chromosome as berrations and junctional regions of rearranged immunoglogulin (Ig) ge nes and T-cell receptor (TcR) genes. The applicability of the immunoph enotyping and PCR-mediated MRD techniques is dependent on the type of leukemia. In virtually all acute lymphoblastic leukemias, PCR analysis of 18 and TcR genes can be used, and immunophenotypic MRD detection i s also possible in 70-80% of cases. In AML, immunophenotypic MRD detec tion can be applied in approximately 80% of cases and PCR analysis of chromosome aberrations in 25-40%. Each MRD technique has its advantage s and limitations, which have to be weighed carefully to make an appro priate choice. Furthermore, standardization of the MRD techniques is n eeded before they are used for stratification or adaptation of treatme nt protocols. Finally, the clinical impact of MRD detection for the va rious subtypes of acute leukemias has to be established.