Of note, mTOR signaling appears to be inhibited in CALR-mutated ET patients, as demonstrated by the downregulation of the mTOR2 complex subunit RICTOR, and of several upstream and downstream factors (i.e., PDK1, PHIP, RHEB, PP2A, and RPS6KB1) (Fig. 2a). This evidence concerns the gene PHIP and essential thrombocythemia.