Fig. 4

Small molecule AI-10-104 can dissociate the IKZFs–RUNXs complex and potentiate the anti-proliferative effect of lenalidomide. a HEK293T cells stably expressing IKZF3 were transfected with constructs encoding an empty vector or FLAG-tagged RUNX1 and treated with increasing amounts of RUNX inhibitor (AI-10-104). Immunoprecipitated FLAG-tagged RUNX1 was probed with antibodies to the indicated proteins. b Same as in (a), except that FLAG-tagged RUNX3 was used. c HEK293T cells stably expressing IKZF1 were transfected with constructs encoding an empty vector or FLAG-tagged RUNX1 and treated with DMSO or 1 μM RUNX inhibitor (AI-10-104). Immunoprecipitated FLAG-tagged RUNX1 was probed with antibodies to the indicated proteins. d Same as in (c), except that FLAG-tagged RUNX3 was used. e Cell counts of the indicated multiple myeloma cell lines grown in media containing the indicated concentration of lenalidomide (L), RUNX inhibitor AI-10-104 (A), and combination (mean ± s.d., n = 3 independent experiments, two-way ANOVA, *P-value ≤ 0.05; **P-value ≤ 0.01; ***P value ≤ 0.001; ****P-value ≤ 0.0001). f Combination indexes (CI) of lenalidomide (L) and RUNX inhibitor AI-10-104 (A) in the indicated multiple myeloma cell lines are shown. Unless otherwise noted, immunoblots are representative of three independent experiments