The loss of autoinhibition of FLT3-ITD leads to phosphorylation (P) of several tyrosines (Y) in the cytoplasmic domain. This leads to constitutive kinase activation, which can be inhibited with FLT3 kinase inhibitors. Methylation (me) of arginines 972 and 973 (R972/R973) by PRMT1 cooperates with phosphorylation at tyrosine 969 (Y969) by enhancing the association with SH2 domains of adaptor proteins such as GRB2. This leads to increased activation of downstream signaling effectors, such as PI3K/AKT and STAT5. PRMT inhibitors prevent methylation of R972/973 and can thereby cooperate with FLT3 inhibitors in blocking activation of downstream signaling pathways.