Mutations in regulators of cell signaling are rare in MPNs and include alterations in SH2B3 (LNK), CBL, NRAS/KRAS, and PTPN11. The known clinical consequences of these alterations are that SH2B3 mutations are associated with shortened survival in ET patients, NRAS/KRAS associates with leukemic transformation and PTPN11 with shortened survival [68,69,70]. The gene discussed is NRAS; the disease is essential thrombocythemia.