Because it was unclear whether compound mutants were sufficient to induce leukemogenesis in CNL, Rohrabaugh et al. recently performed an elegant study demonstrating that CSF3R compound mutations induced aggressive lethal leukemia in mice and that BaF3 cells expressing CSF3R compound mutations in vitro were resistant to both JAK and SRC inhibitors123. The gene discussed is CSF3R; the disease is leukemia.