Myelofibrosis

Myelofibrosis is a myeloproliferative neoplasm characterized by excessive fibrosis (scarring) in bone marrow, leading to anemia, constitutional symptoms, splenomegaly, and increased risk of transformation to acute leukemia. The disease results from clonal proliferation of hematopoietic stem cells, most commonly driven by JAK2, CALR, or MPL mutations. These mutations cause aberrant cytokine signaling, leading to excessive production of fibrogenic cytokines that promote bone marrow fibrosis. As marrow fibrosis increases, normal blood cell production decreases, resulting in anemia, thrombocytopenia, and leukopenia. Extramedullary hematopoiesis develops, leading to massive splenomegaly and hepatomegaly. Constitutional symptoms including fever, night sweats, and fatigue result from elevated inflammatory cytokine levels. Disease burden score systems classify patients into low, intermediate-1, intermediate-2, and high-risk categories based on age, blood counts, symptoms, and genetic features. Median overall survival ranges from 4-5 years for high-risk disease to over 10 years for low-risk disease. Transformation to acute myeloid leukemia occurs in approximately 5-10% of patients.