Targeted In Vivo Infection with a Retroviral Vector Carrying the Interleukin-3 (Multi-CSF) Gene Leads to Immortalization and Leukemic Transformation of Primitive Hematopoietic Progenitor Cells

AbstractTo measure the effect of endogenous IL-3 (Multi-CSF) expression on hematopoietic cells in vivo, we have infected several kinds of hematopoietic cell populations with retroviral vectors carrying the IL-3 gene (M3MuV) in vitro and injected the virus-producing cells into mice to “target” the virus to sites of hematopoiesis. Mast cell lines (Elut cells) or multipotent cell lines (FDC-Pmix) were infected with MPSV-based replication defective retroviral vectors carrying either the neomycin resistance gene alone (M3neoV) or the neomycin gene plus the IL-3 gene (M3MuV). These cell lines produced infective retroviral particles consisting of the replication defective vectors and helper virus constitutively produced by the target cell populations. Irradiated and non-irradiated virus-producing Elut cells and the virus-producing FDC-Pmix cells were transplanted into syngeneic mice to “target” virus infection to the sites of hemopoiesis. Control mice injected with M3neoV-producing cells did not develop a diseas...