Understanding Cancer What Is Primary Myelofibrosis?

MyelofibrosisPrimary myelofibrosis, or MF, is  a chronic blood cancer in which excessive scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells. Researchers believe MF may be caused by abnormal blood stem cells in the bone marrow. The abnormal stem cells produce mature cells that grow quickly and take over the bone marrow, causing both fibrosis (or scar tissue formation) and chronic inflammation. As a result, it becomes more difficult for the bone marrow to create normal blood cells, and blood cell production may move to the spleen, causing enlargement, or to other areas of the body.

Classified as a myeloproliferative neoplasm, or MPN, MF can arise on its own, or as a progression of polycythemia vera (where it is called post-PV-MF) or essential thrombocythemia (where it is called post-ET-MF). The manifestations of MF, post-PV-MF, and post-ET-MF are virtually identical, and treatment is generally the same for all three.

What causes MF?  No one knows exactly what triggers the start of myelofibrosis or other myeloproliferative neoplasms. In the majority of cases, myelofibrosis is not inherited genetically. In other words, you cannot pass the disease on to your children or inherit it from your parents, although some families do demonstrate a clear predisposition. 

Recently, researchers have discovered that these diseases may be caused by acquired gene mutations, or changes in DNA that are not inherited. Some of these mutations affect proteins that work in signaling pathways in your cells.

Risk factors associated with MF include
Age: Myelofibrosis is most often diagnosed in people over the age of 60, although there are known cases of MF in people who are younger.
Environment: Exposure to petrochemicals (such as benzene and toluene) and ionizing radiation may increase the risk of developing MF.
JAK2 Mutation: Approximately 50 to 60 percent of people with MF have a mutation of the JAK2 gene within their blood-forming cells. Mutant JAK2 tells blood cells to grow and divide even when the body is not asking for more blood cells. Between 5 percent and 10 percent of people with MF will have a mutation in another gene named MPL, which also affects the JAK signaling pathway.
CALR: About 23.5 percent of people with myelofibrosis and essential thrombocythemia have a mutation called Calreticulin, or CALR. Research is still ongoing, but there are potential implications for treatments and prognosis for those with the CALR mutation.

Myelofibrosis is most often diagnosed in people over the age of 60, although there are known cases of MF in people who are younger.

How is MF diagnosed?  Physicians review a wide range of factors before making a diagnosis of myelofibrosis. Since every case of MF is different, a medical history, a physical examination, laboratory tests, and a bone marrow examination are usually needed to diagnose the disease.

Even though some people living with myelofibrosis may not have symptoms, or things you feel, they frequently exhibit signs of the disease, things a doctor notices during a physical examination. Common signs of MF during physical examinations may include
• An enlarged spleen 
• Pale mucous membranes, or pallor, if anemia is present
• Loss of muscle mass
• Cachexia, which is a wasting syndrome characterized by weight loss, muscle atrophy, weakness, and fatigue

Routine medical examinations, including complete blood counts, are important for diagnosing MF and other MPNs since some people with MF exhibit no symptoms, especially during the early course of the disease.

What is the prognosis for MF?  There is no single prognosis for people who have myelofibrosis – the prognosis of MF is different for everyone. While some people live for many years without developing major symptoms, others find that the disease progresses more quickly. 

Factors that can influence an MF prognosis are age, white blood cell counts, number of blasts (or immature blood cells) in the blood, constitutional symptoms (such as night sweats, weight loss, and fever), anemia, transfusion dependence, low platelets, and abnormal chromosome analysis. 

For most people, a good MF prognosis requires the management of several symptoms and signs, including
• Anemia 
• Enlarged spleen
• Extramedullary hematopoiesis, or the production of blood cells in organs outside the bone marrow (such as the spleen and liver)
• Thrombosis and blood clotting or bleeding complications
• Leukocytosis (too many white blood cells)
• Thrombocytosis (too many platelets) or thrombocytopenia (low platelet counts)
• Constitutional and systemic, or whole-body, symptoms (such as fatigue, night sweats, weight loss, itching, fever, and bone and joint pain)
• Gout

For a small number of people, MF can transform to acute myeloid leukemia, a serious blood and bone marrow cancer. When AML does arise from MF, it progresses quickly and can be difficult to treat.

What are the available treatments for MF?  There is no single treatment that is effective for all people with MF. Each person has a unique set of symptoms and circumstances that require different treatment options, as prescribed by a doctor. Also, some people with MF stay symptom-free for many years and may not need immediate treatment. However, anyone who has been diagnosed with MF needs to be monitored over time for signs or symptoms that suggest the disease has worsened.

If you’ve been diagnosed with MF, it’s important to know that you’re not alone. The MPN Research Foundation provides comprehensive support. To learn more, visit MPNResearchFoundation.org.

Reprinted with permission from the MPN Research Foundation,
MPNResearchFoundation.org.

This article was published in Coping® with Cancer magazine, September/October 2017.