Background: Primary myelofibrosis is a malignant myeloproliferative disease. It is characterised by proliferation of megakaryocytes in the bone marrow, dysregulated cytokine production and reactive fibrosis that causes bone marrow failure. The purpose of this article is to provide an up-to-date presentation of the pathophysiology, diagnostics and treatment of the disease.
Method: The article is based on the authors' own experience and on a selection of articles identified through many years of experience of treating patients with myelofibrosis.
Results: The molecular mechanisms that trigger the disease remain unidentified, but mutations in two genes (JAK2 and MPL) occur in 70% of patients and result in increased production of haematopoietic cells. Diagnosis is based on clinical examination, bone marrow histology and molecular biological examinations. The clinical course of primary myelofibrosis varies. Life expectancy depends on a number of factors and is severely decreased by high-risk disease. Allogeneic stem cell transplantation is the only treatment with a curative potential, but only a minority of patients are eligible for it. If transplantation is not possible, therapy is symptomatic. JAK2-inhibitors are new drugs that counteract cytokine production and cell proliferation. Ruxolitinib is the first approved JAK2 inhibitor and has proved effective on symptoms and quality of life.
Interpretation: Medical inhibition of the JAK2 gene and associated JAK-STAT signalling pathway is a step forward in treatment. However, stem cell transplantation remains the only potentially curative treatment for myelofibrosis.