The Novel ETS Factor TEL2 Cooperates with Myc in B Lymphomagenesis

Abstract

The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Eμ-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Eμ-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/.

ACKNOWLEDGMENTS

We thank Hiroyuki Kawagoe for providing the MSCV-TEL2-IRES-GFP, MSCV-TEL2-DBDM-IRES-GFP, and MSCV-TEL2ΔPNT-IRES-GFP retroviral vectors and Blake McGourty for the supply of C57BL/6/129svJ mixed-background mice and technical assistance. We also thank the Sherr and Roussel labs for providing Arf and p16^ink4A antibodies. We gratefully acknowledge Ann-Marie Hamilton Easton and Richard Ashmun for expert FACS analysis, and we thank Charlette Hill for editing the manuscript.

This work was supported by NCI grants RO1-CA72999-08 (G.C.G.) and RO1 CA76379-07 (J.L.C.), the Cancer Center (CORE) support grant CA21765, Istanbul University Research Fund project no. 1554/16012001, and by the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital.