Myelofibrosis is a chronic disorder arising from the neoplastic transformation of early hematopoietic stem cells, and is characterized by anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, and portal hypertension.  Myelofibrosis is a rare disorder that affects approximately 1 in 500,000 people worldwide.  It occurs most often in people between 50 and 70 years. 

Diagnosis is based on blood tests that show anemia and the misshapen, immature red blood cells.  Bone marrow biopsy is needed to confirm the diagnosis.  Treatment of myelofibrosis aims to delay the progression of the disorder and to relieve complications.  Drugs and other treatments lessen the severity of anemia, increase red blood cell production, and fight infections.  However, only stem cell transplantation can cure the disorder.  The median survival for patients with primary myelofibrosis is five years from onset, but variation is wide; some patients have a rapidly progressing disorder with short survival and some have a delay in initial diagnosis.  The common causes of death are infections, hemorrhage, cardiac failure, postsplenectomy mortality, and leukemic transformation.

Mutations in the JAK2, MPL, CALR, and TET2 genes are associated with most cases of myelofibrosis.  Approximately 50-60% of patients with myelofibrosis have a gain-of-function mutation in the JAK2 gene, the JAK2 V617F mutation, which leads to increased cytokine responsiveness of myeloid cells.  Another 5-10% of the patients have somatic mutations of JAK2 exon 12 or activating mutations of the thrombopoietin receptor gene MPL.  Mutations in the gene encoding calreticulin (CALR) were present in the majority of patients who lacked mutations in JAK2 or MPL.