Activation of a cellular transforming gene in tumours induced by Abelson murine leukaemia virus

Abstract

Abelson murine leukaemia virus (AbMuLV) is an acutely transforming retrovirus which induces lymphoid neoplasms in mice with latent periods of 3–5 weeks¹. The oncogenicity of AbMuLV is attributed to expression of a viral transforming gene (v-abl) which encodes a protein with tyrosine-specific kinase activity². Two recent findings, however, suggest that oncogenesis by AbMuLV may not be a single-step consequence of v-abl expression. First, Whitlock and Witte³ observed that AbMuLV infection of bone marrow cells in vitro stimulated proliferation of immature blast cells which did not exhibit the in vitro growth properties or tumorigenicity characteristic of cells from AbMuLV-induced neoplasms. These AbMuLV-infected cell populations evolved to fully neoplastic cells only after several weeks in culture, suggesting that secondary events were required for expression of the neoplastic phenotype³. Second, Grunwald et atl.⁴ reported the loss of the AbMuLV genome after prolonged in vivo passage of some AbMuLV-induced neoplasms, suggesting that expression of v-abl may be necessary for initiation, but not maintenance, of transformation. We report here that AbMuLV-induced neoplasms contain cellular transforming genes detectable by transfection which are distinct from AbMuLV sequences. Taken together, these results suggest that v-abl expression may induce early events in the neoplastic process and that secondary activation of a distinct cellular transforming gene may be involved in progression to neoplasia.