Primary myelofibrosis is a rare blood cancer that causes scar tissue to form inside the bone marrow, disrupting the body’s ability to produce healthy blood cells and leading to a range of complications that can significantly affect daily life.

What is Primary Myelofibrosis?

Primary myelofibrosis is a chronic type of bone marrow cancer where excessive scar tissue builds up in the bone marrow, the soft tissue inside bones responsible for making blood cells. This scarring process interferes with the bone marrow’s normal function, making it difficult to produce enough healthy red blood cells, white blood cells, and platelets. As the disease progresses, the body may try to compensate by producing blood cells in other organs, particularly the spleen, which can become enlarged and cause additional problems.^[1][2]

This condition belongs to a group of cancers called myeloproliferative neoplasms, diseases where the bone marrow makes too many abnormal blood cells that don’t function properly. Primary myelofibrosis can occur on its own, or it can develop as a progression of other blood disorders such as polycythemia vera or essential thrombocythemia. When it develops from these other conditions, it’s called secondary myelofibrosis, though the symptoms and treatment approaches are generally similar.^[3][4]

The disease typically progresses slowly over time, and many people may not experience symptoms for years after diagnosis. However, some individuals may experience a more aggressive form that worsens quickly. In approximately 30% of patients, primary myelofibrosis can transform into acute myeloid leukemia, a rapidly progressing and serious form of blood cancer that is difficult to treat.^[5]

How Common is Primary Myelofibrosis?

Primary myelofibrosis is considered a rare disease. According to available data, fewer than 50,000 people in the United States are affected by this condition at any given time.^[8] The disease occurs most frequently in people over the age of 60, though cases have been documented in younger individuals as well. The peak incidence typically falls between 50 and 70 years of age.^[5]

Men appear to be slightly more affected than women. The disease affects individuals predominantly in the male population, though women can also develop the condition.^[5] Because primary myelofibrosis often develops slowly and may not cause symptoms in its early stages, some cases might go undiagnosed for extended periods, potentially affecting the accuracy of incidence statistics.

What Causes Primary Myelofibrosis?

The exact cause of primary myelofibrosis remains unknown. However, researchers have discovered that the disease begins when an early form of blood cell, called a stem cell, undergoes a transformation and becomes cancerous. This cancer cell then makes copies of itself, called clones, which accumulate in the bone marrow. These abnormal cells crowd out healthy blood cells and release substances that damage the bone marrow, leading to the characteristic scarring that defines the disease.^[2][4]

In the majority of cases, primary myelofibrosis is not inherited genetically. People cannot pass the disease on to their children or inherit it from their parents, although some families do show a tendency toward developing the condition.^[3] Instead, the disease appears to be caused by acquired gene mutations, which are changes in DNA that occur during a person’s lifetime rather than being inherited. These mutations affect proteins involved in important signaling pathways within cells.^[3]

The most common genetic mutations found in primary myelofibrosis patients involve the JAK2, CALR, and MPL genes. About 50% to 60% of people with primary myelofibrosis have a mutation in the JAK2 gene. This mutation causes blood cells to grow and divide continuously, even when the body doesn’t need more blood cells. Between 5% and 10% of patients have mutations in the MPL gene, which also affects similar signaling pathways. Approximately 23.5% of patients have mutations in the CALR gene, discovered relatively recently in 2013. About 10% of patients have none of these three mutations, referred to as triple-negative primary myelofibrosis.^[3][5][6]

Who is at Higher Risk?

Several factors can increase a person’s likelihood of developing primary myelofibrosis. Age is the most significant risk factor, with the disease most often diagnosed in people over 60 years old. While the condition can occur in younger people, these cases are far less common.^[3][4]

People who have been diagnosed with other myeloproliferative neoplasms, particularly polycythemia vera or essential thrombocythemia, have an increased risk of eventually developing myelofibrosis as their disease progresses. This progression from one blood disorder to another can occur over time.^[4]

Environmental exposures may also play a role, though these are relatively rare causes. People who have been exposed to high levels of industrial chemicals such as benzene and toluene face increased risk. Similarly, exposure to large doses of ionizing radiation can elevate the likelihood of developing the disease. These environmental factors are uncommon in the general population but represent important considerations for individuals with significant occupational or medical exposures.^[3][4]

Recognizing the Symptoms

Many people with primary myelofibrosis experience no symptoms initially, especially during the early course of the disease. The condition is often discovered during routine blood tests performed for other reasons. When symptoms do appear, they typically develop gradually and worsen over time as the disease progresses.^[3][4]

The most common early symptoms are severe tiredness, weakness, and shortness of breath, especially during physical activity. These symptoms result from anemia, a condition where the body doesn’t have enough red blood cells to carry sufficient oxygen to tissues. Many patients also experience a feeling of fullness, discomfort, or pain in the upper left side of the abdomen, which occurs because the spleen becomes enlarged as it tries to take over blood cell production from the failing bone marrow.^[2][3]

Additional symptoms can include bone pain, which may affect various parts of the body. Joint pain or gout can develop due to changes in how the body processes certain substances. Many patients experience night sweats so severe they wake up drenched in sweat. Fever without an obvious infection, unexplained weight loss or malnutrition, and persistent itching are also common complaints. Some people notice they feel full after eating only a small amount of food, which happens when an enlarged spleen presses against the stomach.^[2][3][4]

Because the bone marrow cannot produce enough platelets, patients may bruise easily or experience unusual bleeding. A shortage of white blood cells makes individuals more susceptible to infections. In later stages of the disease, patients may experience general malaise, problems concentrating, and significant fatigue that interferes with daily activities. Some patients develop an enlarged liver in addition to an enlarged spleen.^[4][5]

Can Primary Myelofibrosis Be Prevented?

Because the exact cause of primary myelofibrosis remains unknown and most cases involve genetic mutations that occur spontaneously during a person’s lifetime, there are no proven methods to prevent the disease. Unlike some other cancers where lifestyle changes or avoiding certain exposures can reduce risk, primary myelofibrosis does not have clear preventable risk factors for most people.^[3]

For individuals with known environmental risk factors, such as occupational exposure to industrial chemicals like benzene or toluene, minimizing or eliminating these exposures may theoretically reduce risk, though this has not been definitively proven. Similarly, avoiding unnecessary exposure to ionizing radiation is generally advisable for overall health, though such exposures are rare causes of the disease.^[3]

For people already diagnosed with polycythemia vera or essential thrombocythemia, regular monitoring and appropriate management of these conditions is important. While this may not prevent progression to myelofibrosis in all cases, it allows for early detection and timely intervention if transformation occurs.^[3]

The most important preventive measure available is regular medical checkups, particularly for individuals over 60 or those with other blood disorders. Routine complete blood count tests can detect abnormalities that may indicate the early stages of myelofibrosis or other blood conditions, allowing for earlier diagnosis and management. Early detection can lead to better outcomes and quality of life, even if the disease itself cannot be prevented.^[3]

How the Disease Affects the Body

Primary myelofibrosis causes significant changes in how the body normally produces and manages blood cells. In a healthy person, bone marrow contains stem cells that develop into mature blood cells: red blood cells that carry oxygen, white blood cells that fight infection, and platelets that help blood clot. In primary myelofibrosis, abnormal stem cells multiply excessively and stimulate cells called fibroblasts to produce too much collagen, a protein that forms scar tissue. This fibrosis, or scarring, gradually replaces the normal bone marrow structure.^[5]

As scar tissue accumulates, the bone marrow loses its ability to function properly. The scarring creates a physical barrier that prevents normal blood cell production. In response, the body attempts to compensate by producing blood cells in places outside the bone marrow, a process called extramedullary hematopoiesis. The spleen and liver are the most common sites for this compensatory blood cell production. This explains why these organs become enlarged in people with myelofibrosis, as they take on a job they weren’t designed to perform efficiently.^[3][5]

The disease also causes chronic inflammation throughout the body, which contributes to many of the constitutional symptoms patients experience, such as fatigue, fever, night sweats, and weight loss. This inflammation results from substances released by the abnormal cells and the body’s immune response to them. The inflammatory state can be debilitating and significantly impacts quality of life.^[3]

As the disease progresses, several complications can develop. The enlarged spleen can become so large it causes severe discomfort and presses on other organs. Blood cell production becomes increasingly inadequate, leading to worsening anemia, increased risk of bleeding from low platelet counts, and greater susceptibility to infections from insufficient white blood cells. Some patients develop increased pressure in the blood vessels connecting the spleen to the liver, which can lead to serious bleeding problems. The abnormal blood cells can also form tumors in various parts of the body, though this is less common.^[4][5]

In the blood, immature blood cells that would normally stay in the bone marrow until they mature are released prematurely into the circulation. Blood tests often show tear-drop shaped red blood cells, a characteristic finding in myelofibrosis. The levels of certain enzymes, such as lactate dehydrogenase, are often elevated. Eventually, bone marrow failure can occur, with severe anemia and thrombocytopenia (low platelet count). The most serious complication is transformation to acute leukemia, which occurs in approximately 30% of patients and represents a medical emergency requiring intensive treatment.^[5]