The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis

Mol Cell Biol. 2005 Mar;25(6):2395-405. doi: 10.1128/MCB.25.6.2395-2405.2005.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • B-Lymphocytes / metabolism
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / metabolism*
  • Cell Proliferation
  • Child
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Suppression, Genetic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Up-Regulation / genetics

Substances

  • DNA-Binding Proteins
  • ETV7 protein, human
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Tumor Suppressor Protein p53