Transformation by v-Myb

Abstract

The v-myb oncogene of the avian myeloblastosis virus (AMV) is unique among known oncogenes in that it causes only acute leukemia in animals and transforms only hematopoietic cells in culture. AMV was discovered in the 1930s as a virus that caused a disease in chickens that is similar to acute myelogenous leukemia in humans (Hall et al., 1941). This avian retrovirus played an important role in the history of cancer research for two reasons. First, AMV was used to demonstrate that all oncogenic viruses did not contain a single cancer-causing principle. In particular, although both Rous sarcoma virus (RSV) and AMV could replicate in cultures of either embryonic fibroblasts or hematopoietic cells, RSV could transform only fibroblasts whereas AMV could transform only hematopoietic cells (Baluda, 1963; Durban and Boettiger, 1981a). Second, chickens infected with AMV develop remarkably high white counts and therefore their peripheral blood contains remarkably large quantities of viral particles (Beard, 1963). For this reason AMV was often used as a prototypic retrovirus in order to study viral assembly and later to produce large amounts of reverse transcriptase for both research and commercial purposes.

Following the discovery of the v-src oncogene of RSV and the demonstration that it arose from the normal c-src proto-oncogene, a number of acute leukemia viruses were analysed by similar techniques and found to also contain viral oncogenes of cellular origin (Roussel et al., 1979). In the case of AMV, it was shown that almost the entire retroviral env gene had been replaced by a sequence of cellular origin (initially called mab or amv, but later renamed v-myb) (Duesberg et al., 1980; Souza et al., 1980). Remarkably, sequences contained in this myb oncogene were shared between AMV and the avian E26 leukemia virus, but were not contained in any other acutely transforming retroviruses. In addition, the E26 virus contained a second sequence of cellular origin (ets) that was unique. The E26 leukemia virus was first described in the 1960s and causes an acute erythroblastosis in chickens, more reminiscent of the disease caused by avian erythroblastosis virus (AEV) than by AMV (Ivanov et al., 1962).