Myelofibrosis

Definition

Myelofibrosis is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly, leading to anemia, cytopenias, and systemic symptoms.

Epidemiology

• Rare disorder with incidence ~0.5–1 per 100,000 per year
• Median age at diagnosis: 60–70 years
• Slight male predominance
• Can be primary (idiopathic) or secondary (post-polycythemia vera or essential thrombocythemia)
• Accounts for a small fraction of myeloproliferative neoplasms

Etiology

• Primary myelofibrosis: idiopathic, associated with JAK2, CALR, MPL mutations
• Secondary myelofibrosis: evolves from polycythemia vera or essential thrombocythemia
• Genetic mutations lead to abnormal hematopoietic stem cell proliferation and marrow fibrosis
• Cytokine dysregulation (TGF-β, PDGF) promotes fibroblast activation and collagen deposition
• Risk factors: age, male sex, prior myeloproliferative neoplasm

Pathophysiology

• Clonal proliferation of abnormal hematopoietic stem cells
• Excessive cytokine release stimulates fibroblast proliferation in marrow
• Bone marrow fibrosis leads to ineffective hematopoiesis
• Extramedullary hematopoiesis in spleen and liver causes organomegaly
• Progressive cytopenias result in anemia, thrombocytopenia, and leukopenia
• Risk of transformation to acute myeloid leukemia in advanced disease