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Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.

The genomic region encoding the miR-17-92 microRNA (miRNA) cluster is often amplified in lymphoma and other cancers, and cancer cells carrying this amplification have higher expression of miRNA in this cluster. Retroviral expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but precisely how higher expression of miR-17-92 promotes lymphomagenesis remains unclear. Here we generated mice with higher expression of miR-17-92 in lymphocytes. These mice developed lymphoproliferative disease and autoimmunity and died prematurely. Lymphocytes from these mice showed more proliferation and less activation-induced cell death. The miR-17-92 miRNA suppressed expression of the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism probably contributed to the lymphoproliferative disease and autoimmunity of miR-17-92-transgenic mice and contributes to lymphoma development in patients with amplifications of the miR-17-92 coding region.

Pubmed ID: 18327259


  • Xiao C
  • Srinivasan L
  • Calado DP
  • Patterson HC
  • Zhang B
  • Wang J
  • Henderson JM
  • Kutok JL
  • Rajewsky K


Nature immunology

Publication Data

April 19, 2008

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI064345
  • Agency: NIAID NIH HHS, Id: R01 AI064345
  • Agency: NIAID NIH HHS, Id: R01 AI064345-01
  • Agency: NIAID NIH HHS, Id: R01 AI064345-02
  • Agency: NIAID NIH HHS, Id: R01 AI064345-03

Mesh Terms

  • Animals
  • Autoimmune Diseases
  • Cell Death
  • Cell Proliferation
  • Cells, Cultured
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Lymphocytes
  • Lymphoma
  • Lymphoproliferative Disorders
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs