例如:"lncRNA", "apoptosis", "WRKY"

Cooperation of ETV6/RUNX1 and BCL2 enhances immunoglobulin production and accelerates glomerulonephritis in transgenic mice.

Oncotarget. 2016 Mar 15;7(11):12191-205
Eva Bauer 1 , Michaela Schlederer 2 , Ruth Scheicher 3 , Jaqueline Horvath 4 , Petra Aigner 1 , Ana-Iris Schiefer 2 , Renate Kain 2 , Heinz Regele 2 , Gregor Hoermann 5 , Günter Steiner 6 , Lukas Kenner 7 , Veronika Sexl 3 , Andreas Villunger 8 , Richard Moriggl 9 , Dagmar Stoiber 4
Eva Bauer 1 , Michaela Schlederer 2 , Ruth Scheicher 3 , Jaqueline Horvath 4 , Petra Aigner 1 , Ana-Iris Schiefer 2 , Renate Kain 2 , Heinz Regele 2 , Gregor Hoermann 5 , Günter Steiner 6 , Lukas Kenner 7 , Veronika Sexl 3 , Andreas Villunger 8 , Richard Moriggl 9 , Dagmar Stoiber 4
+ et al

[No authors listed]

Author information
  • 1 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
  • 2 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
  • 3 Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
  • 4 Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
  • 5 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
  • 6 Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
  • 7 Unit of Pathology of Laboratory Animals, University of Veterinary Medicine, Vienna, Austria.
  • 8 Tyrolean Cancer Research Institute, Innsbruck, Austria.
  • 9 Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria.
全文

摘要


The t(12;21) translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of ETV6/RUNX1 alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. We have previously generated an ETV6/RUNX1 transgenic mouse model where the expression of the fusion gene is restricted to CD19-positive B cells. Since BCL2 family members have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of the antiapoptotic protein BCL2 by crossing ETV6/RUNX1 transgenic animals with Vav-BCL2 transgenic mice. Strikingly, co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice, indicating oncogene cooperativity. This was associated with faster development of follicular B cell lymphoma and exacerbated immune complex glomerulonephritis. ETV6/RUNX1-BCL2 double transgenic animals displayed increased B cell numbers and immunoglobulin titers compared to Vav-BCL2 transgenic mice. This led to pronounced deposition of immune complexes in glomeruli followed by accelerated development of immune complex glomerulonephritis. Thus, our study reveals a previously unrecognized synergism between ETV6/RUNX1 and BCL2 impacting on malignant disease and autoimmunity.

KEYWORDS: BCL2, ETV6/RUNX1, Immune response, Immunity, Immunology and Microbiology Section, autoimmunity, glomerulonephritis, lymphoma