This research focuses on the application of several recently developed molecular genetic techniques to the analysis of clinical and basic problems related to B cell lymphoma and other B lymphocytic neoplasms. A number of projects pertain to immunoglobulin (Ig) gene rearrangements in the diagnosis of B cell neoplasms: (1) Analysis of clonal Ig gene rearrangements will be used to determine whether detection of rearrangements will be useful or a diagnostic criterion for all cases of B cell lymphoma, including cases lacking cellular immunoglobulin. (2) DNA from null cell lymphomas will be examined for Ig gene rearrangements to determine what percentage of these cases are of B cell lineage. (3) Lymphoid tissue from patients with idiopathic thrombocytopenic purpura will be tested for clonal Ig gene rearrangements to ensure that monoclonal immune responses occur rarely, or perhaps never, in an autoimmune disease. (4) Peripheral blood and bone marrow will be screened for clonal Ig gene rearrangements in an effort to detect small numbers of lymphoma cells migrating in the blood, or to monitor minor populations of residual or reemerging neoplastic B cells in the bone marrow of treated patients. A second major portion of this research concerns establishing the incidence of bi- and multiclonal B cell lymphomas in a variety of clinical settings. Evidence for a possible common progenitor stem cell in these cases will be sought by detecting inactivation of the same X chromosome among the multiple tumors of disparate clonal origin from individual female patients. X-inactivation in these clones will be studied by a new approach based on DNA polymorphisms and differences in chromatin structure between active and inactive X chromosomes. Finally, cultured cell lines will be generated from lymphoproliferative lesions arising in immunosuppressed organ transplant recipients. Karyotype and drug sensitivity studies will be performed on these cells, and DNA extracted from these cells and the tumors from which they were originally derived will be utilized in in vitro transformation experiments to identify putative activated oncogenes. (6)
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