Present data describing synergistic activity of mTOR- and JAK/STAT-directed therapies in cellular models of MPN foresee the opportunity of testing this association in clinical trials, with the expectation that such combination might results in a better therapeutic index producing more effective inhibition of clonal cells and also, due to the modest toxicity of mTOR inhibitors against normal cells, by reducing unwanted side effects of JAK2 inhibitors administered at lower, yet effective, dose. The gene discussed is MTOR; the disease is myeloproliferative neoplasm.