shRNA-mediated silencing reveals distinct functions of ETV6/RUNX1 in leukemia

ETV6/RUNX1 (ER) is expressed in 25% of childhood B-cell precursor ALL. It represents not only a first hit mutation but is also necessary for the maintenance of the leukemia phenotype. To confirm and extend our initial studies on the molecular function of the fusion protein, we used a lentiviral-mediated shRNA transfer to target ER. Its depletion led to decreased cellular proliferation and enhanced spontaneous apoptosis in vitro. Moreover, reduction of ER expression delayed engraftment of leukemic cells in a xenotransplant NOD/SCID mouse model, thereby validating its in vivo relevance. RNA expression profiling re…