[The detection of minimal residual disease in leukemia by in vitro DNA amplification]

In vitro amplification of genomic or cDNA sequences by polymerase chain reaction (PCR) is one of the most powerful tools in recent molecular biology. More than 10(5) copies of DNA sequence ranging from 50 bp to 7 kb can be synthesized in a couple of hours. Ever since its development, PCR has attracted much attention because this strategy would allow the detection of minimal residual disease (MRD) at a very low level. The first successful application of this ultra-sensitive technique was the detection of residual tumor cells carrying a 14;18 translocation in follicular lymphoma. The abnormal transcripts caused by 9;22 translocation in chronic myelocytic leukemia (CML) was also exploited for the amplification to detect the MRD. These techniques have successfully shown the detection of one leukemic cell in 100,000 normal cells. Besides leukemic specific sequences caused by chromosome and gene translocations, unique sequences caused by rearrangements in IgH or TCR gamma, delta chain genes have been used as clonal markers for tumor cells. By targetting these sequences for PCR amplification, almost all ALL patients can be analyzed for MRD. The successive measurement of MRD might contribute to improvement of treatments for leukemic patients.