The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis |
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Authors: | Cardone Monica Kandilci Ayten Carella Cintia Nilsson Jonas A Brennan Jennifer A Sirma Sema Ozbek Ugur Boyd Kelli Cleveland John L Grosveld Gerard C |
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Institution: | Department of Genetics, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA. |
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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 Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-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. |
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