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Murine bone marrow cells infected with a novel recombinant retrovirus, MPZen(GM‐CSF), were engrafted into lethally irradiated recipients. The transplanted animals developed extremely high circulating levels of GM‐CSF (up to 3 x 10(5) units/ml), and greatly elevated peripheral nucleated cell counts (up to 110 x 10(6) per ml). Their haemopoietic tissues contained GM‐CSF proviral DNA and produced substantial levels of GM‐CSF. The mice died within 4 weeks of transplantation with extensive neutrophil and macrophage infiltration of the spleen, lung, liver and peritoneal cavity and significant infiltration of both heart and skeletal muscle by neutrophils, macrophages and eosinophils. The thymus and lymph nodes were deficient in lymphoid cells. No disease occurred when infected cells from haemopoietic tissues of the primary transplanted animals were injected into normal or sub‐lethally irradiated mice. Dysregulated GM‐CSF expression by haemopoietic cells thus produces a fatal albeit non‐neoplastic myeloproliferative syndrome.

Murine retroviruses which encode c‐myb proteins that have either complete or truncated carboxy (C) termini were used to infect haemopoietic cells from murine fetal liver. Using an agar colony assay, we could show that infection with the virus encoding the truncated protein resulted in the persistence of colony‐forming cells well beyond the short period for which such cells are present in uninfected cultures. The resultant colonies failed to give rise to cell lines; however, clonal cell lines occasionally emerged from the original infected liquid cultures. The virus which encoded a myb protein with a complete C‐terminus was virtually inactive in the colony assay; surprisingly, however, this virus could enhance proliferation in liquid cultures and has led to the generation of at least one cell line. In addition to demonstrating ‘activation’ of c‐myb by C‐terminal truncation, our results imply that an unaltered c‐myb protein can also contribute to cellular transformation and that a second event is required to establish myb‐transformed cells as a permanent cell line.

To date, cellular transformation in vitro by the myb oncogene has been described for avian haemopoietic cells only. In order to exploit the well‐characterized murine haemopoietic system to study transformation by myb, we have infected fetal liver cells with retroviral vectors carrying cDNAs that encode either complete or carboxy‐terminally truncated c‐myb proteins. We describe four cell lines which, despite our ability to efficiently infect haemopoietic target cells, were generated at low frequency. This was due, as least in part, to the requirement for a rearrangement within the vector that allowed expression of myb sequences. Three of the lines express a truncated myb protein while the fourth apparently expresses a normal c‐myb protein, and thus constitutes an exception to the general association of truncation with transformation by myb. All four cell lines resemble immature cells of the myelomonocytic lineage and are dependent on colony‐stimulating factors (CSFs) for their growth in vitro. One representative line could be converted to CSF‐independence by infection with either Abelson murine leukaemia virus or a recombinant granulocyte‐macrophage‐CSF‐encoding retrovirus; unlike the parental line, the resultant sublines were highly tumorigenic when injected into syngeneic mice.