In vitro approaches to lymphopoiesis, hemopoiesis, and oncogenesis.

Lymphopoiesis still remains a black box. Much remains to be learned about the identification of the cellular stages and the factors that regulate the rate of production of lymphocytes. Modifications of the Dexter system should assist with answers to these questions. Our work on PSF and that of other groups who have studied what is almost certainly the same factor under names such as hemopoietic growth factor, IL-3, BPA or multi-CSF suggests that this factor may provide an alternative means of generating cells for transplantation and replacement therapy. At present the only established sources of PSF are the activated T cell or tumors in which we think the gene has been anomalously activated, such as WEHI-3B; the long-term bone marrow culture system, however, seems to be defining a factor or influence that may be identical with, or is able to replace, the T cell factor. Finally, our experiments with the heterogeneous P cell lines and the initiation of oncogenesis by activation of the PSF gene raise some caveats about the use of cultured cells for human therapy. In the mouse system the production of immortalized factor-dependent lines appears to be more frequent in cells taken from long-term bone marrow cultures rather than normal bone marrow. Obviously, further information on the mechanism of immortalization and on the frequency and mechanism of activation of PSF genes in such lines will be of great importance in guiding the practical use of in vitro-derived cells and in the understanding of leukemogenesis.