Isolation of immortal cell lines from the first stage of murine leukemia virus-induced leukemia.

Friend murine leukemia virus (F-MuLV) is a replication-competent retrovirus that induces a rapidly fetal leukemia in susceptible mice (stage I disease). Leukemia cells obtained from these animals do not grow in cell culture using standard tissue culture conditions. However, in the presence of WEHI-3 cell-conditioned medium (CM), 100% of spleen or bone marrow explants from diseased mice yield immortal cell lines. These cell lines exhibit the same growth properties, produce the same viruses, and express the same oncogenes as the leukemia cells found in mice with stage I disease. No cell lines were obtained from leukemic mice in the absence of CM. No cell lines were obtained from uninfected adult, newborn, or phenylhydrazine-treated animals with or without CM. We conclude that some of the hematopoietic cells in F-MuLV-diseased mice will proliferate indefinitely in the presence of CM. The development of this abnormal response to CM is one of the early changes associated with F-MuLV-induced leukemia.