The immediate goal of this study is to utilize two novel techniques, Primer-directed DNA Sequence Amplification and Reverse Transcriptase- mediated mRNA Sequence Amplification, to detect and quantify minimal residual cells carrying the t(14;18). The ultimate goals are to determine the biological significance of minimal residual circulating cells carrying the t(14;18), to assess the clinical usefulness of these two powerful techniques and to eventually define cure with a quantitative assay. The study will be conducted primarily in a prospective manner. All the newly diagnosed lymphoma patients who have the t(14;18) within the major breakpoint region will be candidates for study. Blood samples will be collected sequentially a) prior to therapy, b)during clinical remission, c) until disease relapses clinically. The samples will be simultaneously analyzed by Souther Blot Analysis, Primer-directed DNA Sequence Amplification Assay and Reverse Transcriptase-mediated mRNA Sequence Amplification Assay. The results will be correlated with subtypes of histopathology, initial Ann Arbor clinical stage, clinical status at the time sample was obtained, duration of remission and survival. A retrospective study also will be performed in a highly selected group of patients with follicular lymphoma who have been in continuous remission for more than two year even though the structure of the bcl-2 gene in the pretreatment samples was not studied. Our study will help in understanding the natural history and mechanism of disease recurrence in lymphomas with the t(14;18) and defining the prognostic significance of minimal residual cells carrying the t(14;18). We also propose to address the question as to whether there are dormant cells carrying the t(14;18). This will be determined by studying whether such cells can be found in patients in long term remission and whether they are transcribing the bcl-2/IgH mRNA. These sequence amplification assays will be modified to make them quantitative. These quantitative results will be correlated with the clinical outcome to eventually define """"""""cure"""""""".
| Lee, M S; Stass, S A (1993) Uses of polymerase chain reaction in leukemia: detection of minimal residual disease and identification of novel genetic mutations. Cancer Treat Res 64:35-44 |
| Lee, M S (1993) Molecular aspects of chromosomal translocation t(14;18). Semin Hematol 30:297-305 |
| Soubeyran, P; Cabanillas, F; Lee, M S (1993) Analysis of the expression of the hybrid gene bcl-2/IgH in follicular lymphomas. Blood 81:122-7 |
| Lee, M S; Wang, J C; Beran, M (1992) Two independent amsacrine-resistant human myeloid leukemia cell lines share an identical point mutation in the 170 kDa form of human topoisomerase II. J Mol Biol 223:837-43 |
