The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis.
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.
Cardone
Monica
M
Department of Genetics, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Kandilci
Ayten
A
Carella
Cintia
C
Nilsson
Jonas A
JA
Brennan
Jennifer A
JA
Sirma
Sema
S
Ozbek
Ugur
U
Boyd
Kelli
K
Cleveland
John L
JL
Grosveld
Gerard C
GC
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D004268:DNA-Binding Proteins; C409823:ETV7 protein, human; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53
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