Mutations can change the function of a protein and thus be the driver of diseases. In this video, Omar Abdel-Wahab, MD, from the Memorial Sloan Kettering Cancer Center, New York, NY, discusses mutations in RNA splicing factors that have been identified in patients with leukemia, highlighting these exciting new therapeutic targets. This video was recorded at the International Conference on Acute Myeloid Leukaemia 2017 in Estoril, Portugal by the European School of Hematology (ESH).