Retroviral transfer and expression of the interleukin-3 gene in hemopoietic cells.

A recombinant retrovirus containing the interleukin-3 (IL3) coding sequence and the neomycin-resistance gene (Neor) has been generated. Infection of fetal liver cells with the IL3 retrovirus, but not with the N2 parental virus, resulted in the formation of factor-independent, NeoR colonies containing various types of differentiated hemopoietic cells. Established cell lines could be generated from these mixed hemopoietic colonies. These cell lines contained the unrearranged viral genome, produced viral IL3, and secreted the growth factor; however, they were not tumorigenic. Identical results were obtained from infection of two factor-dependent cell lines with the IL3 virus, except that these clones all became tumorigenic. These data indicate that endogenous IL3 production can support normal differentiation and immortalization of primary hemopoietic cells, or, in previously immortalized cells, can lead to tumorigenicity.