Model for MLL fusion-mediated noncanonical Wnt signaling leading to Rac activation. MLL fusions induce Frat1 and Frat2 gene expression. The FRAT1 protein promotes canonical Wnt signaling by binding and inactivating GSK3 and disrupting the β-catenin destruction complex. FRAT2 promotes activation of Rac GTPases, in a pathway requiring DVL expression and GSK3 activity. Activation of RHO and CDC42 by DVL and Rac by the RAS/RAF and PI3K pathways is also indicated. FRAT proteins thereby coordinate the differential requirement of GSK3 in canonical and noncanonical signaling pathways that are essential for the oncogenicity of MLL fusion proteins in AML.