To demonstrate a role for IL-21 in the treatment of AML, we treated MLL-AF9 AML mice with overt leukemia daily with 20 μg recombinant mouse (rm)-IL-21 or vehicle in a 5 days on and 2 days off treatment schedule and assessed survival. 20 μg rm-IL-21 has previously been shown to affect tumor growth in syngeneic cancer models.29 Here, KMT2A is linked to acute myeloid leukemia.