MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

研究的目的是试图理解这种机制

Studies have been aimed at trying to understand the mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more stages of the malignant process. Studies on the acute erythroleukemia-inducing spleen focus-forming virus (SFFV) have concentrated on understanding how this virus abrogates the erythropoietin (Epo) requirement of erythroid cells. The unique envelope glycoprotein encoded by SFFV has been shown to be responsible for this biological effect and we now show using molecular recombinants between variants of SFFV that sequences present in the transmembrane domain of the viral envelope glycoprotein are essential for rendering the cells Epo-independent. Studies designed to understand the mechanism by which SFFV alters the Epo requirements of erythroid cells should be aided by our recent observation that an Epo-dependent erythroleukemia cell line can be rendered Epo-independent by infection with SFFV. As previously shown with spleen cells from SFFV-infected mice, the induction of factor-independence in these cells by SFFV does not appear to involve a classical autocrine mechanism involving Epo. The factor-independent cells, however, eventually acquire the ability to produce a unique growth factor that may contribute to their growth. Using the Epo-dependent erythroleukemia cell line and its SFFV-infected counterpart, we can find no evidence of induction of protein tyrosine phosphorylation by either Epo or SFFV. Studies on the genetics of susceptibility to erythroleukemia induced by Friend MuLV continue to concentrate on the Rmcf locus, which encodes or regulates the expression of an MCF-related envelope glycoprotein. Our recent data indicate that this protein may be encoded by a modified polytropic provirus that is present in Rmcfr mice but not Rmcfs mice. In other studies, we show that the Rmcf gene also effects susceptibility to the thymic lymphoma induced by Moloney MuLV.