Abstract
Primary myelofibrosis (PMF) is a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) driven primarily by the constitutive activation of the Janus associated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. The approval of ruxolitinib, a JAK inhibitor in 2011 revolutionized the treatment of PMF in terms of symptom palliation and incremental survival in a selected subgroup of advanced patients. Nevertheless, currently available treatments for PMF have not demonstrated the ability to halt disease progression and the quest for rationally targeted treatment options in PMF is an ongoing research endeavor. In this chapter we review the current understanding of the pathogenesis of myelofibrosis (MF), prognostic models, and novel therapeutics that may very well change the current treatment paradigm. In addition to MF, we also review the current biological understanding of a related MPN, chronic neutrophilic leukemia (CNL), as well as the clinical and therapeutic aspects of this rare hematologic malignancy.