Overview

Primary myelofibrosis is a chronic bone marrow disorder classified among the myeloproliferative neoplasms (MPNs). It is characterized by abnormal proliferation of hematopoietic stem cells that disrupt normal marrow architecture, leading to replacement of marrow spaces by fibrous tissue and to blood count abnormalities. The disease is uncommon and most often affects adults.

Causes and pathophysiology

The condition arises from a clonal expansion of marrow precursor cells. Frequently identified molecular alterations include mutations in JAK2, CALR or MPL, which affect signaling pathways controlling blood cell production. Excessive proliferation of megakaryocytes and other progenitors stimulates fibroblasts and extracellular matrix deposition, producing marrow fibrosis and prompting blood formation outside the marrow (extramedullary hematopoiesis).

Clinical features and complications

Symptoms vary from mild to severe. Common manifestations include fatigue and pallor from anemia; a large, often painful spleen (splenomegaly); night sweats, weight loss, and fevers; and bruising or bleeding when platelet function is impaired. Important complications are progressive cytopenias, increased risk of thrombosis, portal hypertension from massive splenic enlargement, and possible transformation to acute myeloid leukemia.

Diagnosis

Evaluation combines clinical assessment with laboratory and tissue studies. Typical tests and findings include:

  • Complete blood count showing anemia, variable white cell and platelet counts.
  • Peripheral blood smear with teardrop-shaped red cells and immature precursors.
  • Bone marrow biopsy demonstrating increased reticulin or collagen fibrosis and atypical megakaryocytes.
  • Molecular testing for driver mutations (JAK2, CALR, MPL) and cytogenetic studies to aid risk assessment.

Treatment and prognosis

Treatment focuses on symptom control, managing complications and altering disease course when possible. Options include transfusion support, drugs to reduce splenomegaly and symptoms (for example JAK inhibitors), cytoreductive agents, and interferon in selected patients. Allogeneic hematopoietic stem cell transplantation can be curative for some but carries substantial risks. Prognosis is heterogeneous and is assessed with clinical scoring systems that inform therapeutic decisions and follow-up.

History and notable facts

The disorder has been described under several names historically, including idiopathic or chronic myelofibrosis; modern classifications place it within the spectrum of myeloproliferative neoplasms. Research continues into targeted therapies, molecular predictors of outcome, and strategies to prevent progression to acute leukemia.