A JAK of all trades: how global phosphoproteomics reveal the Achilles heel of MPNs

Abstract

While Janus-kinase (JAK)-inhibitors effectively reduce the inflammatory phenotype of myeloproliferative neoplasms (MPN), they do not affect disease burden or presence of the mutated clone to a major extent. Here, we show how Janus-kinase 2 (JAK2)-mutated cells persist through maintenance of the mitogen-activated protein kinase Interacting Serine/Threonine Kinase 1 (MKNK1)–Extracellular Signal-regulated Kinase (ERK)-axis by hijacking the splicing machinery through post-translational modifications.