The MN1-TEL fusion protein, encoded by the translocation (12;22)(p13;q11) in myeloid leukemia, is a transcription factor with transforming activity

The Tel gene (or ETV6) is the target of the translocation (12;22)(p13;q11) in myeloid leukemia. TEL is a member of the ETS family of transcription fac tors and contains the pointed protein interaction (PNT) domain and an ETS D NA binding domain (DBD), By contrast to other chimeric proteins that contai n TEL's PNT domain, such as TEL-platelet-derived growth factor beta recepto r in t(5;12)(q33;p13), MN1-TEL contains the DBD of TEL. The N-terminal MN1 moiety is rich in proline residues and contains two polyglutamine stretches , suggesting that MN1-TEL may act as a deregulated transcription factor. We now show that R MN1-TEL type I, unlike TEL and MN1, transforms NIH 3T3 cel ls. The transforming potential depends on both N-terminal MN1 sequences and a functional TEL DBD. Furthermore, we demonstrate that MN1 has transcripti on activity and that MN1-TEL acts as a chimeric transcription factor on the Moloney sarcoma virus long terminal repeat and a synthetic promoter contai ning TEL binding sites. The transactivating capacity of MN1-TEL depended on both the DBD of TEL and sequences in MN1, MN1-TEL contributes to leukemoge nesis by a mechanism distinct from that of other chimeric proteins containi ng TEL.