In the present study, we demonstrated that Msi2 silencing decreased proliferation, induced cell cycle arrest in G0/G1 phase, and increased apoptosis in AML cell line Dami, HL-60, and primary AML cells from patients with AML, which were attributed to suppression of Akt, Erk1/2 and p38 phosphorylation. This evidence concerns the gene MAPK3 and acute myeloid leukemia.