Common Myelofibrosis Symptoms & Causes – Described by Patients

Myelofibrosis (MF) is a form of bone marrow cancer that impacts your body’s ability to produce blood cells at an average rate. Understanding myelofibrosis symptoms and causes can help you identify if you are at risk for MF and if you may be experiencing some of the symptoms commonly linked to the disease.

While the cause of myelofibrosis is not fully known, it is linked to the mutations of the JAK2, MPL, CALR, and TET2 Genes.

The disease is part of a group of cancers of the bone marrow known as myeloproliferative neoplasm (MPNs). More generally, MF is considered chronic leukemia, a form of cancer that impacts the blood-forming tissues. Therefore, the symptoms and complications of MF are primarily associated with either the overproduction or lack of production of blood cells.

What are the Symptoms of Myelofibrosis?

As with most myeloproliferative neoplasms, symptoms of myelofibrosis are almost non-existent during the early stages of the disease. However, the symptoms will become more apparent as the disease progresses into its more advanced stages.

Some common symptoms of myelofibrosis include:

• Abdominal pain
• Decreased appetite
• Enlarged spleen
• Fatigue
• Lightheadedness
• Anemia
• Pale skin
• Frequent infections
• Bone or joint pain
• Night sweats
• Excessive itching (pruritus)
• Bleeding or bruising easily
• Shortness of Breath

What Causes Myelofibrosis?

The underlying cause of myelofibrosis is not fully understood yet. However, according to the Cleveland Clinic, myelofibrosis has been associated with mutations of the following genes:

• Janus kinase 2 (JAK2) – about 50% of patients
• Myeloproliferative leukemia (MPL) – 5% to 10% of patients
• Calreticulin (CALR) – 35% of patients
• Tet methylcytosine dioxygenase 2 (TET2) – frequency in MF patients TBD

Both the JAK2 and MPL genes provide the instructions for making proteins to promote the division and growth of blood cells. Mutations of both genes lead to an overactivation of the JAK/STAT pathway. This results in an overproduction of megakaryocytes, the hemopoietic cells that lead to the production of blood cells. 

While the overproduction of blood cells is a problem in itself, megakaryocytes also stimulate a different type of cell to release collagen. Typically collagen helps provide structural support to the cells in the bone marrow. However, when produced in abundance, the collagen forms scar tissue in the bone marrow.

The CALR gene is responsible for providing the instructions for making a protein that has multiple functions. In comparison, the TET2 gene provides the instructions for the production of a protein whose function is unknown. Further research is necessary to identify how the mutation of the CALR and TET2 genes are involved in the development of myelofibrosis.

Is Myelofibrosis Hereditary?

According to the MPN Research Foundation, myelofibrosis is rarely inherited genetically, meaning you cannot inherit the disease from your parents, nor are you likely to pass the gene on to your children. Instead, the disease typically occurs as the result of a gene mutation, a change in your DNA during your lifetime, not an inherited trait. 

Can Someone Have Myelofibrosis without a Gene Mutation?

It is possible for an individual with myelofibrosis not to have one of the above-listed mutations. While researchers believe that other genetic mutations may cause the disease, the genes have yet to be identified.

Can Myelofibrosis Develop from Other Diseases?

Secondary myelofibrosis is when MF forms as the result of another disease. Occasionally other myeloproliferative neoplasms (MPNs) like polycythemia vera (PV) or essential thrombocythemia (ET) can progress into myelofibrosis.

What are the Risk Factors for Myelofibrosis?

While the cause of myelofibrosis is unknown, a few factors are linked to an increased risk for myelofibrosis. Some of these risk factors include:

• Age – Those over the age of 60 are typically at the highest risk of a MF diagnosis. 
• Chemical exposure – myelofibrosis has been linked with repeated exposure to certain industrial chemicals such as toluene and benzene.
• Other blood disorders – as mentioned earlier, those with PV or ET risk developing the disease into MF.
• Radiation exposure – exposure to extremely high radiation levels increases the risk of MF.

If you fit into one of the risk categories, it does not mean you will have myelofibrosis. However, it is important to get blood work on at least a yearly basis to track potential indicators of the disease.

Source: lls.org

Myelofibrosis Complications

A few severe complications may result from myelofibrosis to be aware of. Unlike symptoms, which may be temporary and potentially result from some other issue, these complications are a direct result of myelofibrosis.

Portal Hypertension

An enlarged spleen can lead to an increased blood flow into the liver. Blood enters the liver through the portal vein. If the blood pressure is too high in the portal vein, it can force excess blood into the smaller veins in your stomach or esophagus. This extra blood can cause the veins to rupture, leading to internal bleeding. 

Tumors

The excess blood cells in your body can eventually form clumps outside the bone marrow. The clusters of blood cells can cause tumors to grow in other areas of your body, resulting in many complications depending on the tumor’s location. 

Acute Myeloid Leukemia (AML)

Approximately 10% to 20% of people with myelofibrosis develop acute myeloid leukemia, a severe and aggressive form of cancer.

Thrombocytopenia

As myelofibrosis progresses into its advanced stages, the bone marrow becomes scarred, causing blood platelet counts to fall below normal. With an insufficient number of platelets (thrombocytopenia), you bleed much more easily than average. This is essential to consider when accessing surgery risks or even managing day-to-day cuts.