Introduction to a review series on the new wave of targeted therapeutics for MPNs

Abstract

Ruxolitinib and subsequent JAK2 inhibitors have improved care for some patients with the myeloproliferative neoplasms myelofibrosis, essential thrombocythemia (ET), and polycythemia vera, but major problems remain and there is much to do. This Review Series, curated by Associate Editor Jason Gotlib, covers 3 areas where exciting advances are occurring. Gotlib’s editorial sets the scene for these by summarizing where we are in 2026 and lessons from how we got here. Constantinescu, Vainchenker, and Pecquet discuss how new ways to switch off JAK signaling are delivering a suite of new small-molecule drugs with potential. Salzman and Mullally review the biology of calreticulin mutations in myelofibrosis and ET and how multiple different modalities can be brought to bear against this mutant surface protein, including monoclonal antibodies, bispecific T-cell engagers, and cellular and vaccine therapies. Finally, Kremyanskaya, Ginzburg, and Hoffman outline the major recent progress being made in controlling excessive erythropoiesis through pharmacological modulation of iron metabolism.