V-MYB AND V-ETS TRANSFORM CHICKEN ERYTHROID-CELLS AND COOPERATE BOTH IN TRANS AND IN CIS TO INDUCE DISTINCT DIFFERENTIATION PHENOTYPES

E26 is an acute avian leukemia virus that encodes the transcriptional activator oncogenes v-myb and v-ets in a single fusion protein. This virus is also unique in that it is able to transform hematopoietic cells of both the myeloid and the erythroid lineage. To determine the contributions of v-myb and v-ets to the transforming potential of the virus, derivatives expressing separate Myb and Ets proteins, either alone or in combination, were constructed. We found that in the myeloid lineage v-myb, but not v-ets, induces cell transformation. In the erythroid lineage both v-myb and v-ets weakly transform erythroblast-like cells. These cells exhibit a mature phenotype and a low self-renewal capacity. The transforming efficiency of the two oncogenes is enhanced if they are coexpressed as separate proteins or as a fusion protein, the transformed cells displaying an increased self-renewal capacity. Interestingly, however, cells transformed by the Myb-Ets fusion protein have a distinct phenotype in that they are very immature. These results demonstrate that v-myb and v-ets can cooperate in the transformation of erythroid cells both in trans and in cis and that the mode of cooperation is reflected by the differentiation phenotypes of the transformed cells.