In addition to candidate approaches such as targeting known downstream components of JAK2 signaling and epigenetic regulators (e.g., AKT, mTOR, PIM, PRMT5, LSD1, among others) [49, 51, 52, 56–63], less candidate-centric approaches, including phosphoproteomics [64], interrogation of JAK2 persistence in MPN mouse models [65] as well as gain of function genetic screens [66] have been used to identify potential mechanisms of JAK2 inhibitor persistence. This evidence concerns the gene AKT1 and myeloproliferative neoplasm.