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Isolation of immortal cell lines from the first stage of murine leukemia virus-induced leukemia
Abstract:
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.
Insights
Friend murine leukemia virus (F-MuLV) causes leukemia in mice. In vitro, F-MuLV leukemia cells require conditioned medium (CM) for immortalization, indicating an early disease change.
Area of Science:
- Retroviral pathogenesis
- Hematopoietic stem cell biology
- Cancer cell line development
Background:
- Friend murine leukemia virus (F-MuLV) is a retrovirus that causes rapid leukemia in susceptible mice.
- Leukemia cells from F-MuLV-infected mice do not proliferate under standard cell culture conditions.
Purpose of the Study:
- To investigate the in vitro growth requirements of F-MuLV-induced leukemia cells.
- To determine if specific culture conditions can induce immortalization of leukemia cells.
Main Methods:
- Spleen and bone marrow explants from F-MuLV-diseased mice were cultured.
- Cultures were supplemented with WEHI-3 cell-conditioned medium (CM) or lacked CM.
- Explants from uninfected or treated control mice were also cultured under similar conditions.
Main Results:
- 100% of explants from F-MuLV-diseased mice yielded immortal cell lines in the presence of CM.
- These immortalized cell lines retained the biological and virological characteristics of the original leukemia cells.
- No cell lines were obtained from leukemic mice without CM or from any control animals.
Conclusions:
- Certain hematopoietic cells from F-MuLV-diseased mice exhibit indefinite proliferation in response to CM.
- This abnormal response to CM is an early event in the development of F-MuLV-induced leukemia.