Pairing JAK with MEK for improved therapeutic efficiency in myeloproliferative disorders.

The identification of JAK2 mutations as disease-initiating in myeloproliferative neoplasms (MPNs) has led to new and effective therapies for these diseases. In a study published in this issue of the JCI, Stivala et al. explored the key observation that JAK inhibition successfully suppresses MAPK activation in MPN cell lines and primary MPN cells in vitro, and the finding that it failed to completely and effectively suppress MAPK activation in vivo in two mouse models. The authors went on to show that dual inhibition of JAK and the MAP kinase pathway provided enhanced therapeutic efficacy in the in vivo models of MPN.