Constitutive activation of JAK2 in MPN drives multiple downstream pathways, including the signal transducer and activator of transcription (STAT) 3/STAT5, mitogen-activated protein kinases (MAPK), extracellular signal–regulated kinase (ERK) and Phosphatidylinositol 3-kinase (PI3)/Akt/Mammalian target of Rapamycin (mTOR) pathways 5–8. The gene discussed is PI3; the disease is myeloproliferative neoplasm.