INDUCTION OF B-CELL LYMPHOMAS BY OVEREXPRESSION OF A MYB ONCOGENE TRUNCATED AT EITHER TERMINUS

The c-myb oncogene encodes a nuclear transcriptional transactivator th at is often terminally truncated in hematopoietic tumors. To directly assess the tumorigenic activity of full length and terminally-truncate d variants of c-myb, we have overexpressed several structurally-altere d forms of myb within an avian retroviral vector and have shown that o verexpression of truncated (but not full length) myb transforms both m yeloid cells in vitro and mesenchymal cells in vivo. In vivo infection with these truncated myb viruses is now shown to induce metastatic B cell lymphomas in a significant minority of animals. Evaluation of the lymphomas revealed two distinct mechanisms of myb-induced tumorigenes is. In most of the lymphomas, proviral DNA inserted into the endogenou s chicken c-myb gene and promoted the expression of a 5'-truncated myb transcript encoding an amino terminal truncated protein. In compariso n, some animals infected with a virus encoding a carboxyl (C) terminal truncated myb (T-myb) developed non-insertional B cell lymphomas that directly expressed the provirally-encoded T-myb gene. The lymphomagen ic T-myb protein lacks 214 C terminal amino acids including all of the myb transcription inhibition domain, This novel lymphomagenic activit y for a C terminal truncated myb suggests that a loss of regulatory se quences at either end of c-myb is sufficient to create a B cell-specif ic transforming gene.