The novel findings of a significant synergism exerted in vivo by combination of BEZ235 and ruxolitinib, that we report herein by using both a leukaemia model in immunodeficient mice injected with Ba/F3 cells harbouring JAK2V617F mutation and a JAK2V617F KI mouse model closely mimicking human MPN, give further strong support to the potential therapeutic relevance of dual JAK2 and PI3K/mTOR inhibition. Here, MTOR is linked to myeloproliferative neoplasm.