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ETV6 and ERG: Two PNT Domain ETS Transcription Factors, Contrasting Roles in Leukemogenesis
Shai Izraeli 1
1Schneider Children’s Medical Center, Tel Aviv University, Israel
ETV6 and ERG are two highly related transcription factors characterized by a PNT protein-interaction domain and an ETS DNA binding domain. Both function in hematopoietic stem cell development and maintenance and in development of the myeloid and lymphoid lineages. Yet, they play contrasting roles in leukemogenesis. ETV6 is a tumor suppressor and its inactivation, by mutations or chromosomal translocations, leads to leukemias. I will present data demonstrating that recruitment of the histone acetylase P300 to ETV6 in early myeloid cells induces a lymphoid developmental program leading to biphenotypic myeloid – lymphoid acute leukemia. In contrast, ERG is an oncogene activated by chromosomal translocations in Ewing Sarcoma, Prostate cancer and, rarely in leukemia. ERG induces acute myeloid or lymphoid leukemias through its recruitment or induction by leukemia associated oncogenic complexes. We show that interaction of ERG with repressor complexes is required for its leukemogenic activity and that treatment with HDAC3 inhibitors suppress ERG dependent myeloid and lymphoid leukemias as well as prostate cancer.
Supported by Israel Science Foundation, Israel Cancer Research Fund, Waxman Cancer Research Foundation and the Dotan Center for Hematological Malignancies, Tel Aviv University.