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Pathogenetic mechanisms in primary myelofibrosis

Ayalew Tefferi, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Alan G Rosmarin, MD


Primary myelofibrosis [1-3] (PMF, chronic idiopathic myelofibrosis, agnogenic myeloid metaplasia) is one of the chronic myeloproliferative neoplasms, which are collectively characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency (table 1).

The primary disease process in PMF is a clonal hematopoietic stem cell disorder that results in chronic myeloproliferation and atypical megakaryocytic hyperplasia [4]. The secondary process of bone marrow fibrosis (BMF) is the result of nonclonal fibroblastic proliferation and hyperactivity induced by growth factors abnormally shed from clonally expanded megakaryocytes [5]. BMF is the hallmark of PMF and contributes to the impaired hematopoiesis that leads to severe anemia. In addition to BMF and anemia, patients with PMF suffer from marked splenomegaly, extramedullary hematopoiesis, and severe constitutional symptoms. (See "Clinical manifestations and diagnosis of primary myelofibrosis".)

The potential to arrest or reverse the BMF in PMF may offer an alternative approach to palliative therapy. With this goal in mind, the pathogenesis of PMF will be discussed here. The prognosis and treatment of PMF are discussed separately. (See "Management of primary myelofibrosis".)


The exact cause of primary myelofibrosis (PMF) is unknown. PMF, along with the other chronic myeloproliferative disorders, chronic myeloid leukemia, polycythemia vera, and essential thrombocythemia, is considered to arise from a somatic mutation of a pluripotent hematopoietic progenitor cell [6,7]. A defective stem cell "niche" within the bone marrow has been postulated for PMF [8]. (See "Overview of the myeloproliferative neoplasms".)

The occurrence of PMF has, in a minority of cases, been linked to exposure to thorium dioxide, petroleum manufacturing plants (especially toluene and benzene), and ionizing radiation [6,9,10]. A very high incidence of PMF has been noted in patients given thorium-based radiographic contrast material and in individuals exposed to atomic bombs at Hiroshima [11,12].

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Literature review current through: Nov 2017. | This topic last updated: Nov 03, 2016.
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