A truncated RARα co-operates with the v-erbB oncogene to transform early haematopoietic progenitors in vitro and in vivo

Abstract

We have shown recently that a retrovirus vector expressing a natural mutant form of the PML-RARα protein characteristic of human acute promyelocytic leukaemia can transform early chicken hematopoietic progenitors (Altabef et al., 1996). Neither truncated PML nor truncated RARα alone could induce transformation which suggest that the two domains should co-operate for the oncogenicity of the fusion product. To further investigate the mechanisms of this co-operation, we have tested whether a truncated RARα could co-operate with the v-erbB oncogene. This oncogene has previously been shown to co-operate with the rearranged thyroid hormone receptor, v-erbA, to transform erythrocytic progenitors. We show that v-erbB and a truncated RARα co-operate when expressed simultaneously as independent products to transform very early chicken haematopoietic cells close to pluripotent stage. In addition, we show that v-erbB alters transcriptional abilities of RARα by both enhancing its effects on RARE and reducing those on AP-1. Therefore, RARα is able to co-operate with different kinds of proteins to induce transformation of early haematopoietic cells. This strongly suggests that RARα are involved in the differentiation commitment of early haematopoietic progenitors during the normal process of haematopoietic differentiation. These data bring new insights in the mechanisms of oncogenic transformation by rearranged RARα.