Both conditional knockout and small-molecule inhibitor studies reveal that loss of PRMT5 has anti-tumor activity against MLL-rearranged acute myeloid leukemia (AML) likely due to hypomethylation of essential splicing factor like SRSF1 [54,55], and further vulnerability of cancer to PRMT5 loss is bestowed on the tumors that harbor driver mutation in splicing factors [56]. Here, KMT2A is linked to acute myeloid leukemia.