Causes and Risk Factors
For most people who have myelofibrosis (MF), there are no obvious reasons (risk factors) why they developed the disease. The disease starts as one of two other myeloproliferative diseases, either polycythemia vera or primary thrombocythemia, in about 10 percent to 15 percent of people with MF.
Doctors don't fully understand the cause of MF. About half of all patients with MF have a mutation (change in their DNA) called "V617F JAK2" (Janus kinase 2) found in the JAK2 gene. This mutated gene may play a role in MF's onset. However, researchers are still studying its precise role as the cause of the disease.
Between 5 and 10 percent of MF patients will have a myeloproliferative leukemia (MPL) gene mutation. Like JAK2, this gene is also the subject of research to determine what role it plays in MF development.
How Does MF Develop?
MF results from a mutation in a stem cell in the bone marrow, which leads to uncontrolled blood cell production. Abnormal cell production gradually overtakes production of normal red cells, white cells and platelets. Too few red cells are made, and usually too many platelets and white cells are made. Eventually, there are more abnormal cells in the marrow than there are normal cells.
An important constant feature of MF is the production of too many "megakaryocytes," the term for the giant cells in the marrow that break up into fragments and produce hundreds to thousands of platelets. This leads to the release of chemicals called "cytokines" in the marrow. The cytokines stimulate the development of scar tissue in the marrow, called fibrosis.
The platelets' normal function is to stick to the site of a blood vessel injury and form a plug (clot) to seal off the injured blood vessel to stop bleeding. The body makes new platelets to replace used platelets. The megakaryocytes can become so abnormal that platelet production decreases in some patients.
Myelofibrosis gets its name from the disease's characteristics. The prefix "myelo-" in the word "myelofibrosis" means a relationship to the marrow. The presence of scar tissue gives the disease the "fibrosis" part of its name. MF is also known by several other names, including agnogenic myeloid metaplasia and idiopathic myelofibrosis.
Source: Myelofibrosis Facts Reviewed by Ayalew Tefferi, MD.