Dagmar Stoiber and her colleagues report an unexpected autoimmunity-phenotype in mice expressing the oncogene ETV6/RUNX1. The translocation generating the ETV6/RUNX1 fusion gene represents the most frequent chromosomal rearrangement in childhood leukemia. Presence of this fusion alone is usually not sufficient for leukemia onset, and additional genetic alterations have to occur in ETV6/RUNX1-positive cells to cause transformation. In ETV6/RUNX1 transgenic mice the expression of the fusion gene is restricted to CD19-positive B cells. Since family members of the antiapoptotic protein BCL2 have been proposed to play a role in leukemogenesis, we investigated combined effects of ETV6/RUNX1 with exogenous expression of BCL2. Co-expression of ETV6/RUNX1 and BCL2 resulted in significantly shorter disease latency in mice. 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.
We congratulate Dagmar Stoiber and her colleagues to this nice success.