Detection of acute myeloid leukemic cells in complete remission and in extramedullary sites by clonal analyses

We report the case of a 49-year-old woman with acute myeloid leukemia (AML, M5b). The leukemic cells expressed blast as well as myelomonocytic antigens and were characterized by a clonal gene rearrangement of the immunoglobulin (Ig) JH gene. During the course of the disease in clinical/cytological complete remission (CR) the persistence of leukemic cells was shown by surface marker analyses on bone marrow (BM) cells or BM clones grown in agar. Moreover, clonal leukemic cells could be detected by Southern blot analyses indicating the persistence of blasts. Occasionally BM cells obtained in CR showed a cytologically, immunologically differentiated phenotype, but nevertheless DNA-rearranged cells indicated differentiated blasts ('clonal remission'). Five years after diagnosis the patient presented with an isolated pleural effusion. Southern blot analysis identified the original leukemic clone because pleural cells showed the same clonal Ig gene rearrangement as the cells at diagnosis. The patient died 6 years after diagnosis during her fourth relapse of AML. This shows the value of Southern blot analyses, immunophenotyping and culture techniques to monitor the course of leukemic tumor burden even if it is not cytologically identifiable.