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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2016

AutorInnen: Bauer, E; Schlederer, M; Scheicher, R; Horvath, J; Aigner, P; Schiefer, AI; Kain, R; Regele, H; Hoermann, G; Steiner, G; Kenner, L; Sexl, V; Villunger, A; Moriggl, R; Stoiber, D

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

Quelle: Oncotarget. 2016; 7(11):12191-12205



Autor/innen der Vetmeduni Vienna:

Kenner Lukas
Moriggl Richard
Scheicher Ruth
Sexl Veronika

Beteiligte Vetmed-Organisationseinheiten
Institut für Tierzucht und Genetik, Abteilung für Funktionelle Krebsgenomik
Institut für Pathologie, Abteilung für Labortierpathologie
Institut für Pharmakologie und Toxikologie


Abstract:
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 Pubmed: Animals
Core Binding Factor Alpha 2 Subunitgeneticsimmunology
Glomerulonephritisgeneticsimmunology
Humans
Immunoglobulinsbiosynthesisimmunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proto-Oncogene Proteins c-bcl-2biosynthesisimmunology
Proto-Oncogene Proteins c-etsgeneticsimmunology
Repressor Proteinsgeneticsimmunology

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