The detection of post-therapy residual minimal disease in leukemias characterized by specific chromosomal anomalies

Chromosomal and Southern Blot analyses have been used to diagnose Leukemias characterized by non-random chromosomal rearrangements. They have also been used to monitor disease progression during and after chemotherapy. These methodologies are often not adequate to detect RMD after ablative therapy and Bone Marrow Transplantation (BMT). Molecular quantitative Polymerase Chain Reaction (PCR) techniques have been developed to detect low levels of leukemic cells in patients with diseases characterised by fusion transcripts. 95% of Chronic Myelocytic (CML) and 15-25% of Acute Lymphoblastic Leukemia (ALL) patients are Ph1 producing a fusion transcript between the abl proto-oncogene and the bcr gene. Acute Promyelocytic Leukemia (APL) with break points in the (RAR) gene and the zyl gene also produces a fusion transcript. The significance of PCR for 1) detecting RMD after therapy, 2) correlating low levels of leukemic cells over time with therapeutic response and long term remission and 3) assessing the effect of RMD during remission by sequential analyses is discussed.