October 23, 2008
View Full PaperPrimary Myelofibrosis: Update on Definition, Pathogenesis, and Treatment
Key Points
- The aim is to update the understanding of primary myelofibrosis concerning its definition, pathogenesis, and treatment options.
- Review of recent literature on primary myelofibrosis
- Analysis of JAK2 and MPL mutation roles in pathogenesis
- Assessment of newly developed targeted therapies
- Majority of PMF patients have a recurrent mutation in the JAK2 gene.
- Activating mutations in the MPL gene were found in a subset of patients.
- Insight into targeted therapy development based on genetic mutations is emerging.
Abstract
Primary myelofibrosis (PMF) is a clonal stem cell disorder that manifests clinically as anemia, splenomegaly due to extramedullary hematopoiesis, leukoerythroblastosis, and constitutional symptoms, which are the clinical hallmarks of PMF. Within the past three years it has been determined that a single, recurrent, somatic mutation in the gene encoding the cytoplasmic tyrosine kinase Janus kinase 2 (JAK2) occurs in the majority of patients with PMF, and more recently, activating mutations in the gene encoding the thrombopoietin receptor MPL have also been identified in a subset of PMF patients. These discoveries have yielded important insights into the pathogenesis of PMF and have brought about the first opportunity for rationally targeted therapy for this disorder. Here we present an updated review of the pathogenesis, definition, and treatment of PMF in light of the discovery of JAK2 and MPL mutations, as well as other recent work in the myeloproliferative neoplasm field.