[Molecular diagnosis in hematopoietic malignancy]

Molecular analysis of leukemias has been demonstrated to be useful for understanding the pathogenesis of leukemias or for detection of minimal residual disease. We present studies on the application of molecular diagnosis in malignant lymphomas. Although follicular lymphomas, a part of non-Hodgkin's lymphomas (NHL), often involve a t (14;18) chromosomal translocation, it is difficult to detect the translocation in some cases by conventional chromosomal analysis. We showed the usefulness of amplification of mbr/JH and mcr/JH junction by PCR to detect the translocation. The PCR products of mbr/JH junction were positive in 7 out of 8 cases of follicular lymphomas some of which were negative in tests on the translocation in the malignant cells. However, most NHL do not have cytogenetically specific translocations, indicating the necessity for another way to diagnose the malignant lymphomas. We used IgH gene probes as tumor specific markers in B-cell lineage malignant lymphomas. We determined DNA sequences for complementarity-determining region 3 (CDR3) of IgH in the malignant clone of each case. Then, we prepared a unique 5' primer for PCR or an oligonucleotide probe for detecting the clone-specific VH gene in each case, amplified the DNA by PCR and finally tried to detect minimal disease in bone marrow or peripheral blood, which brought into sequential detection of minimal residual disease in NHL. Thus, molecular diagnosis in hematopoietic malignancy will be more important in diagnosis, staging, and clinical management of patients with NHL.