Primary Myelofibrosis is a rare blood disorder that causes scarring of the bone marrow and mutated blood stem cells. This illness affects about 1 in 500,000 people and has recently been classified as a type of chronic leukemia due to its effects on the blood-forming tissues in the body. The cause of primary myelofibrosis is mainly unknown, but doctors have been able to trace myelofibrosis to the janus kinase 2, or the Jak2 gene. This is the specific gene that becomes mutated and causes overproduction of the specific blood cell megakaryocyte.
The megakaryocyte stimulates another cell in the bone marrow to release collagen, and the extra collagen in the bone marrow which creates scarring. Myelofibrosis is usually caused by somatic mutation or a mutation that is not inherited, although genetic inheritance has been recorded. This illness can cause anemia, enlarged spleen, enlarged liver, weakness, fatigue, and can turn into acute leukemia. The liver and spleen become enlarged because the scarred bone marrow is unable to produce blood cells. So in attempt to keep the body healthy, the liver and spleen start producing blood cells which causes them to swell.
There are a several risk factors for contracting myelofibrosis. Age: primary myelofibrosis is primarily diagnosed in people aged 50-80. Another blood disorder: some patients may develop myelofibrosis from complications of other blood disorders. Chemical exposure: exposure to toluene and benzene has been linked to patients with myelofibrosis. Radiation exposure: it has been found that people who have been exposed to high radiation levels have a greater chance of acquiring myelofibrosis.
Myelofibrosis is slow to progress and usually goes unnoticed for years. In its early stages, typically there are not any symptoms making it hard to detect. A biopsy of the bone marrow can give confirmation of the illness. If there are no symptoms showing, treatment is not necessary. Since there is currently no cure for myelofibrosis, treatment only targets the symptoms of the illness and not the illness itself.
The FDA just recently approved a drug called ruxolitinib or better known as Jakafi. This medication acts by stopping all JAK related genes in the body slowing the symptoms of myelofibrosis. On the downside of Jakafi, healthy cells are also affected along with the mutated cells causing lower platelets and red blood cells. This can cause increased bruising, infection, blood loss, dizziness, and headaches. Blood transfusions may be required if anemia is present from the illness. A couple of other options to treat the anemia are androgen therapy and thalidomide.
Androgen therapy is taking a synthetic version of the male hormone androgen which may promote the production of red blood cells. Thalidomide is a medication that can also promote the production of red blood cells but can have more moderate side effects than androgen therapy. If the spleen enlargement is causing complications and other methods of therapy failed, surgical removal of the spleen may be necessary. Chemotherapy and radiation can also be used to decrease the size of the spleen but they also have high risks of severe side effects.
The only chance of a potential cure to myelofibrosis is an allogeneic stem cell transplant. But again, this also has a high risk of life threatening complications/side effects. Before getting the actual transplant, a patient has to go through large levels of radiation and chemotherapy to kill the diseased bone marrow. The high doses of chemotherapy and radiation also kill the immune system which gives greater chance for graft versus, host disease and other infections. Doctors are currently studying a new transplant technique called a nonmyeloablative transplant, also known as a mini transplant. The idea of a nonmyeloablative transplant is to use lower doses of radiation and chemotherapy to help cope with the life threatening side effects. Although the mini transplant is still dangerous, doctors are hoping that one day it will be a safer alternative.
References
“Primary Myelofibrosis.” Genetics Home Reference. 24 Apr. 2012. Web. 30 Apr. 2012. <http://ghr.nlm.nih.gov/condition/primary-myelofibrosis>.
Staff, Mayo Clinic. “Definition.” Mayo Clinic. Mayo Foundation for Medical Education and Research, 13 Dec. 2011. Web. 30 Apr. 2012. <http://www.mayoclinic.com/health/myelofibrosis/DS00886>.
