Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ DEFINITION ++ Primary myelofibrosis is a chronic clonal myeloid disorder that originates in mutations in a multipotential hematopoietic cell. The disease is characterized by (a) anemia, (b) splenomegaly, (c) increased CD34+ cells, immature granulocytes, erythroid precursors, and teardrop-shaped red cells in the blood, (d) marrow fibrosis and increased dysmorphic megakaryocytes, and (e) osteosclerosis. ++ EPIDEMIOLOGY ++ Onset characteristically after age 50 years. Median age at diagnosis approximately 68 years. Adult males and females affected equally. Incidence about 1.0 case per 100,000 in persons of European descent. ++ PATHOGENESIS ++ Origin in the neoplastic transformation of a multipotential hematopoietic cell. In approximately 50 percent of cases, the hematopoietic cells (blood cell lineages) contain the mutation JAK2 V617F. In approximately 10 percent of cases, the hematopoietic cells contain a mutation in the MPL gene, which encodes the thrombopoietin receptor. Constitutive mobilization and circulation of CD34+ cells as a result of epigenetic methylation of the CXCR4 promoter, leading to decreased expression of CXCR4 on CD34+ cells and their enhanced migration from marrow to blood. CD34+ cells in this disorder generate about 24-fold the megakaryocytes in culture than do CD34+ cells from normal persons. ++ Fibroplasia ++ Reticulin fibers (type III collagen), as detected by silver staining, are increased in the marrow in most patients. Fibrosis may progress to thick collagen bands (type I collagen) identified with the trichrome stain. Increased plasma concentrations of procollagen III amino-terminal peptide, prolylhydroxylase, and fibronectin are present. The extent of fibrosis is correlated with the prevalence of dysmorphic megakaryocytes and release of fibroblast growth factors from the megakaryocyte α granules (e.g., platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-β, and others). The fibroblastic proliferation in the marrow is a reaction to the cytokines released by an increased density of dysmorphic megakaryocytes, not an intrinsic part of the clonal expansion of hematopoietic cells. Thicker bands of collagen fibrosis (type I collagen) may develop as the marrow fibrosis advances. ++ CLINICAL FEATURES ++ The median age at diagnosis is approximately 68 years, but the disorder may occur at any age. The sex incidence is equal in adults, but twice as many females as males in young children. Rarely, myelofibrosis is preceded by extended exposure to benzene or very high-dose ionizing radiation. Approximately 25 percent of patients are asymptomatic at time of diagnosis. Fatigue, weakness, shortness of breath, palpitations, weight loss, night sweats, and bone pain are common presenting symptoms. Wasting, peripheral edema, or bone tenderness may occur. Left upper-quadrant fullness, pain or dragging sensation, left shoulder pain, and early satiety may result from splenic enlargement and/or infarction. Splenomegaly is present in virtually all patients at the time of diagnosis and is massive in one-third of cases. Hepatomegaly is present in two-thirds of patients. Neutrophilic dermatosis (Sweet syndrome) may be present. ++ SPECIAL CLINICAL FEATURES +... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!