Management of Myeloproliferative Neoplasms in the Molecular Era: From Research to Practice

The 1960 discovery of the Philadelphia chromosome in chronic myeloid leukemia (CML) marked the beginning of the modern genomic era of oncology. In the following years, the molecular underpinnings of CML were unraveled, culminating in the development of the first molecularly targeted therapy: imatinib. Imatinib revolutionized CML management, inducing deep molecular responses for most patients and aligning survival curves with those of age-matched control participants. Five additional tyrosine kinase inhibitors are now approved for CML: dasatinib, nilotinib, bosutinib, ponatinib, and asciminib (approved October 2021). The 2005 discovery of JAK2 mutations in myelofibrosis (MF) sparked enthusiasm that molecularly targeted therapies could have a similar impact in that disease. Three JAK inhibitors are now available for MF: ruxolitinib, fedratinib, and pacritinib (approved February 2022). JAK inhibitors are helpful for improving symptoms and splenomegaly but still only scratch the surface of MF pathophysiology. Clinical research testing novel agents, next-generation JAK inhibitors, and combinations of JAK inhibitors plus novel agents is moving at a tremendous pace in the hope that outcomes for patients with MF may mirror those with CML one day. This review provides an update on the status of clinical care and research for MF and addresses ongoing issues related to CML management.