Myelofibrosis
Primary myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm driven by JAK2, CALR, or MPL mutations that produces marrow fibrosis, extramedullary hematopoiesis, massive splenomegaly, and a leukoerythroblastic smear with teardrop cells. Diagnosis rests on bone marrow biopsy showing fibrosis with a clonal marker or exclusion of reactive causes, and management is risk-stratified with the JAK inhibitor ruxolitinib for symptomatic disease and allogeneic transplant as the only cure.
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What this article covers
- Overview
Definition: primary myelofibrosis (PMF) is a clonal, BCR-ABL-negative myeloproliferative neoplasm (MPN) in which proliferating megakaryocytes drive marrow fibrosis and extramedullary hematopoiesis…
- Epidemiology
Disease of older adults: typically presents in the sixth to seventh decade of life, consistent with its status as a clonal stem cell disorder acquired over time.
- Risk factors
JAK2 V617F mutation: present in about half of patients with PMF and the most common identifiable driver.
- Pathophysiology
Clonal megakaryocyte proliferation is the initiating event: the malignant clone produces atypical, hyperplastic megakaryocytes that secrete cytokines, chiefly transforming growth factor beta-1 (TGF-beta1).
- Clinical features
Massive splenomegaly: occurs in virtually all patients and is the hallmark physical finding, producing abdominal fullness, early satiety, and left upper quadrant pain or discomfort; hepatomegaly…
- Differential diagnosis
Chronic myeloid leukemia: marked leukocytosis with a full spectrum of granulocyte maturation stages, but defined by the Philadelphia chromosome/BCR-ABL fusion, which is never present in myelofibrosis (chronic myeloid leukemia).
- Diagnosis
Diagnosis is established by bone marrow biopsy demonstrating extensive marrow fibrosis, together with a clonal marker (JAK2, CALR, or MPL mutation) or exclusion of secondary causes of marrow fibrosis…
- Management
Observe asymptomatic, low-risk patients: no treatment is needed until symptoms, worsening cytopenias, or disease progression develop; monitor with periodic clinical assessment and blood counts.
- Complications
Transformation to acute myeloid leukemia: a recognized progression of PMF and other BCR-ABL-negative MPNs, usually refractory to therapy and associated with a poor prognosis.
- Prognosis
DIPSS risk group is the primary determinant of survival: low-risk disease has an estimated overall survival in the 15-year range, while high-risk disease carries a median survival of only about 16 months.
- Prevention
No modifiable risk factor prevents primary myelofibrosis, since it arises from an acquired somatic clonal mutation (JAK2, CALR, or MPL); prevention efforts instead focus on avoiding treatment-related harm and catching complications early.
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