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. Sequences present in the transmembrane domain of the viral envelope protein were found to be essential for rendering the cells Epo-independent. In addition to causing erythroleukemia in mice, SFFV also can efficiently and reproducibly render an erythropoietin-dependent cell line factor-independent. The induction of factor independence does not appear to involve a classical autocrine mechanism, but may be due to the interaction of an SFFV-encoded protein with the Epo receptor. In other studies, it was shown that the inefficiency with which the Akv helper virus introduces SFFV into erythroid target cells is due to a 304 bp region of its envelope gene. Studies on the genetics of susceptibility to erythroleukemia induced by Friend MuLV have shown that DNA from mice carrying the Rmcf(r) locus contain a unique provirus, related to a modified polytropic virus, that is not present in the DNA from Rmcf(s) mice. In other studies, it was shown that the Rmcf gene does not effect susceptibility of mice to thymic lymphoma induced by Moloney MuLV. Studies on the effects of the ME26 virus, which contains both the myb and ets oncogenes, on hematopoietic cells have shown that Epo-dependent cell lines can easily and reproducibly be derived from the spleens of ME26-infected mice. The Epo-dependent cells are morphologically distinct from SFFV and F-MuLV-induced erythroleukemia lines and resemble early erythroid precursors or stem cells.