- Is a rare bone marrow cancer. It is one of a related group of blood cancers known as “myeloproliferative neoplasms (MPNs)” in which bone marrow cells that produce the blood cells develop and function abnormally. The resulting fibrous scar tissue formation in the bone marrow leads to severe anemia, weakness, fatigue, an enlarged spleen and liver, and body wasting (loss of body mass or size).
- Is a type of chronic leukemia and can occur on its own (primary myelofibrosis) or as a result of another bone marrow disorder. Other MPNs that can progress to myelofibrosis include polycythemia vera and essential thrombocythemia.
What You Should Know
- Hematologists and oncologists are specialists who treat people who have myelofibrosis (MF) or other types of blood cancer.
- MF usually develops slowly and some people may live symptom-free for years. Others, however, may get progressively worse, requiring treatment. In both cases, patients do need to be monitored regularly.
- The treatment goal for most patients with MF is to relieve symptoms, reduce an enlarged spleen, improve blood cell counts (i.e., anemia), and reduce the risk of complications.
What You Should Do
- Talk with your doctor about your diagnostic tests and what the results mean.
- Talk with your doctor about all your treatment options and the results you can expect from treatment.
- Ask your doctor whether a clinical trial is a good treatment option for you.
How Does MF Develop?
The DNA (genetic material) of a single hematopoietic (blood-forming) stem cell is damaged. This is called an “acquired mutation.”
- Stem cells form blood cells (white cells, red cells and platelets).
As the mutated blood cell replicates and divides, it passes along the mutation to new cells. Eventually, this abnormal cell production overtakes the bone marrow’s ability to produce enough normal blood cells, including
- Red blood cells, which carry oxygen to the tissues
- White blood cells, which fight infection
- Platelets, which help blood to clot.
When the bone marrow is unable to make enough healthy blood cells, the result can be severe anemia, weakness, bone pain, fatigue and increased risk of infection or bleeding.
- The abnormal growth of blood-forming cells can also take place outside of the bone marrow, called “extramedullary hematopoiesis,” in such organs as the liver, spleen, lungs, lymph nodes and spinal cord, causing swelling.
An important constant feature of MF is the overproduction of platelet-forming cells, called "megakaryocytes," in the marrow. This causes too many platelets to be released into the blood and chemicals called “cytokines” to be released into the marrow. The cytokines stimulate the development of scar tissue in the marrow, called fibrosis. Paradoxically, the number of megakaryocytes can become so abnormal that platelet production decreases in some patients.
- Platelets are small blood cells (comprising about one-tenth the volume of red cells) that stick to the site of a blood vessel injury and form a plug to seal off the injured blood vessel to stop bleeding. Normally, new platelets are made to replace used platelets in the body.
- 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.
About 90 percent of people with MF have a mutation (a change in their DNA) in one of three genes (JAK2, CALR or MPL). All three of these gene mutations cause abnormal signaling in the JAK pathway, which regulates blood cell production.
- About 50 percent of patients have the“V617F JAK2” mutation found in the JAK2 gene
- About 25 percent have a mutation in the calreticulin (CALR) gene,
- Between 5 and 10 percent of MF patients have a myeloproliferative leukemia (MPL) gene mutation.
- In addition, over last several years, mutations in many other genes, such as ASXL1, EZH2, IDH1/2, SRSF2 and TET2 have been found in 5 to 20 percent of patients with MF; these mutations may occur in addition to JAK2, CALR, or MPL mutations, and one person may have several of them at the same time.
The reason genetic mutations occur in MF is unknown. Exposure to petrochemicals, such as benzene and toluene, and ionizing radiation may raise the risk of developing the cancer. But only a small proportion of people exposed to these chemicals develop MF. A theory about why MF develops in some people is that they have inherited genes that limit their ability to detoxify the causative agents. In most cases, MF is not an inherited disease, but there are some rare cases of familial clustering of the MPNs, including MF. There is no known prevention.
Source: Myelofibrosis Facts. Reviewed by Srdan Verstovsek, MD, PhD.