In summary, we demonstrated that double cleavages at the breakpoints of BCR and ABL1 genes by the CRISPR/Cas9 system generate a balanced translocation that mimics the Ph chromosome in a human factor-dependent leukemia cell line, indicating that simultaneous DSBs at the BCR and ABL1 breakpoints could be initiation events in Ph+ leukemia oncogenesis. The gene discussed is ABL1; the disease is leukemia.