Neoplastic proliferation and natural history of B-cell neoplasia.
In this analysis, I have concentrated on advances in immunology, kinetics, and clinical oncology which have provided a substantial basis for identifying major common features in the natural history and pathophysiology of B-cell neoplasia as diverse as MM, MG, BMG, and NL. Observations on the natural history of both experimental and clinical myeloma as well as studies of kinetics of proliferation of MM and BMG in man provide the basis for reasonable hypotheses. Firstly, malignant variants of B-cell neoplasms may result from a two-hit evolution. In this scheme, the first hit is a triggering by specific antigen which leads to a required monoclonal expansion, while the second hit is the oncogenic event. Some cases of BMG seem to be examples of an unusually prolific response to the first hit, while others appear to be minimal deviation malignancies after the second hit. In this latter circumstance, the neoplastic clone in BMG usually retains a significant degree of sensitivity to tumor mass-related feedback inhibition. This may occasionally be lost during subsequent subcloning. Significant future testing of these hypotheses may prove feasible through the application of the in vitro tumor colony-forming assay system as it lends itself to study of a number of the salient features of these disorders.
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D002455:Cell Division; D005246:Feedback; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology; D007136:Immunoglobulins / Q000096:biosynthesis; D007700:Kinetics; D008223:Lymphoma / Q000209:etiology* / Q000473:pathology; D009101:Multiple Myeloma / Q000209:etiology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000209:etiology; D008258:Waldenstrom Macroglobulinemia / Q000209:etiology
D007136:Immunoglobulins