Myelofibrosis is a rare blood cancer that disrupts the bone marrow’s ability to produce healthy blood cells. This condition causes scar tissue to gradually replace normal bone marrow, making it difficult for your body to maintain normal blood cell levels. While the disease progresses slowly in many people, understanding its causes, symptoms, and risk factors can help you navigate life with this condition more effectively.

Epidemiology

Myelofibrosis is an uncommon condition that affects a relatively small number of people worldwide. In the United States, approximately 16,000 to 18,500 individuals are living with this disease at any given time^[5]. This makes it one of the rarer blood cancers, which means that many healthcare providers may have limited experience treating patients with this specific condition.

The disease primarily affects older adults, with most people receiving their diagnosis around the age of 65^[5]. People in their 50s and 60s are more likely to develop myelofibrosis than younger individuals^[7]. While it can occur in younger people, cases in young adults or children are rare. The condition can affect both men and women, though specific gender patterns have not been definitively established in the available research.

Because myelofibrosis is uncommon, many patients may feel isolated or struggle to find others with similar experiences. This rarity also means that diagnosis may take longer, especially in the early stages when symptoms are minimal or absent.

Causes

The exact cause of myelofibrosis remains unknown to medical researchers. What scientists do understand is that the disease begins in the bone marrow, the soft, spongy tissue inside your bones where blood cells are made^[1]. Something triggers the earliest form of a blood cell, called a stem cell, to transform into a cancer cell^[2].

When this transformation happens, the abnormal stem cell begins to multiply rapidly, creating malignant copies of itself. These cancer cells crowd out the healthy blood cells that your body needs. They also release substances that damage your bone marrow, leading to scarring inside your bones^[2]. This scarring process is called fibrosis, which is where the disease gets its name.

Although researchers don’t know what triggers this process in the first place, they have identified genetic changes that are commonly found in people with myelofibrosis. Many patients have mutations in genes called JAK2, CALR, or MPL^[2]. These mutations affect how cells communicate and grow. Approximately 50 to 60 percent of people with myelofibrosis have a mutation called JAK2V617F^[3][12]. Another 23.5 percent have a mutation in the CALR gene^[3], while about 5 to 10 percent have changes in the MPL gene^[3][12].

These genetic mutations are not inherited from your parents in most cases. In the majority of situations, you cannot pass the disease on to your children or inherit it from your parents, though some families do show a clear predisposition to developing blood disorders^[3].

Myelofibrosis can develop on its own, which is called primary myelofibrosis. Sometimes it develops as a progression of other blood conditions, such as essential thrombocythemia or polycythemia vera^[2]. When this happens, it is called secondary myelofibrosis. The manifestations and treatment of both types are virtually identical^[3].

Risk Factors

Several factors can increase your chances of developing myelofibrosis, though having one or more risk factors does not mean you will definitely develop the disease. Age is the most significant risk factor. People over 60 are at increased risk, and the disease is most often diagnosed in individuals over 50^[2][3].

Environmental exposures play a role in some cases. People who have been exposed to industrial chemicals such as benzene and toluene may have a higher risk of developing myelofibrosis^[3][7]. Similarly, exposure to high levels of ionizing radiation can increase risk, though this is rare in most populations^[2][7].

Having another blood cell disorder significantly increases your risk. If you have been diagnosed with primary thrombocytosis or polycythemia vera, you face a higher likelihood of developing myelofibrosis over time^[2][7]. These conditions are part of a group of disorders called myeloproliferative neoplasms, where the bone marrow makes too many blood cells.

The presence of the JAK2 mutation is also considered a risk factor^[7]. This genetic change appears in blood-forming cells and tells blood cells to grow and divide even when the body is not asking for more cells.

Symptoms

Many people with myelofibrosis have no symptoms at first, especially during the early course of the disease^[3]. This is why the condition is sometimes discovered during routine medical examinations or blood tests done for other reasons. When the disease begins to interfere with blood cell production, symptoms may emerge slowly over time.

The first symptoms to appear are usually severe fatigue and an enlarged spleen. Fatigue is caused by anemia, which means having a low red blood cell count^[2]. Red blood cells carry oxygen throughout your body, so when you don’t have enough of them, you may feel tired, weak, or short of breath even with mild exertion. An enlarged spleen may feel like heaviness or fullness in your upper left abdomen, under the left ribs^[2]. This area may also hurt or cause discomfort after eating.

Other common symptoms include bone and joint pain, which can be persistent and uncomfortable^[2][3]. Many people experience night sweats that can be severe enough to wake them up feeling covered in sweat^[1]. Fever may occur even without an infection. Unexplained weight loss is another symptom that concerns many patients^[2].

Some individuals develop easy bruising or bleeding because their platelet counts are abnormal^[1][2]. Platelets are blood cells that help your blood clot, so having too few can lead to bleeding problems. People with myelofibrosis may also get infections more easily because their white blood cell function is impaired^[2].

Itching of the skin is a frustrating symptom for many patients^[2][3]. This itching, called pruritus, can be intense and difficult to relieve. Feeling full quickly when eating is common because the enlarged spleen takes up space in your abdomen^[3]. Problems with concentration can occur, making it harder to focus on daily tasks^[2].

As the disease progresses, some people may develop an enlarged liver in addition to the enlarged spleen^[2]. In more advanced cases, abnormal blood cell production may occur outside the bone marrow in other organs, causing additional complications^[3].

Prevention

Unfortunately, there are no known methods to prevent myelofibrosis because the exact cause of the disease is not fully understood. Since genetic mutations that occur during a person’s lifetime play a role, and these are not inherited in most cases, traditional prevention strategies do not apply.

However, if you know you have risk factors, there are steps you can take to potentially reduce your risk or catch the disease early. If you have been diagnosed with essential thrombocythemia or polycythemia vera, regular monitoring by your healthcare provider is important. These conditions can evolve into myelofibrosis over time, so staying in close contact with your medical team allows for early detection of any changes.

Avoiding exposure to industrial chemicals like benzene and toluene whenever possible may help reduce risk^[3][7]. If you work in an environment where these chemicals are present, following all safety protocols and using proper protective equipment is important.

Routine medical examinations, including complete blood counts, are important for detecting myelofibrosis and other blood disorders, especially if you are over 50 or have other risk factors^[3]. Early detection may not prevent the disease, but it can help you start treatment sooner if needed.

Maintaining overall health through a balanced diet, regular physical activity, and avoiding smoking can support your body’s ability to cope with health challenges, though these measures have not been proven to prevent myelofibrosis specifically.

Pathophysiology

Understanding what happens inside your body when you have myelofibrosis can help you make sense of your symptoms and treatment. The disease is classified as a myeloproliferative neoplasm, which means it causes your body to make too many abnormal blood cells that don’t work correctly^[1].

The process begins when an early stem cell in your bone marrow undergoes a genetic change. This transformed cell becomes a cancer cell that multiplies rapidly. The cancer causes inflammation inside your bone marrow, which triggers the formation of scar tissue, or fibrosis^[2]. As more scar tissue builds up, the bone marrow loses its ability to produce healthy blood cells.

The abnormal stem cells produce mature cells that grow quickly and take over the bone marrow space. This crowding effect pushes out the normal blood-forming cells. Additionally, these abnormal cells release substances that directly damage the bone marrow structure, accelerating the scarring process^[7].

When your bone marrow becomes too scarred to function properly, your body tries to compensate. Your spleen and sometimes your liver attempt to take over blood cell production, a process called extramedullary hematopoiesis^[2]. This is why the spleen becomes enlarged, a condition called splenomegaly. As your spleen works overtime to filter abnormal blood cells and produce new ones, it can grow significantly larger than normal.

The genetic mutations commonly found in myelofibrosis, particularly in JAK2, CALR, and MPL genes, cause abnormal activation of cell signaling pathways. These pathways normally tell cells when to grow and divide. When they’re constantly activated due to mutations, cells receive signals to grow even when the body doesn’t need more blood cells^[5].

The JAK-STAT pathway is particularly important. Janus-associated kinases, or JAKs, are proteins that tell blood cells in the bone marrow to divide and grow. When JAKs are working normally, they help the body make the right number of blood cells. But when JAKs aren’t working normally due to mutations, they cause the body to make the wrong number of blood cells. They can also contribute to bone marrow scarring, an enlarged spleen, and various symptoms^[5].

As the disease progresses, your body may not produce enough red blood cells, leading to anemia and fatigue. White blood cell and platelet counts may be higher or lower than normal, depending on the stage of the disease^[14]. The abnormal blood cells that are produced often don’t function properly, which is why people with myelofibrosis are more prone to infections, bleeding, and blood clots.

High levels of inflammatory substances called cytokines circulate in the blood of people with myelofibrosis. These substances contribute to many of the constitutional symptoms like night sweats, fever, weight loss, and bone pain^[12].

In some cases, myelofibrosis can progress to transform into acute myeloid leukemia, the most aggressive form of leukemia^[2][11]. This transformation occurs when the disease becomes more aggressive and blood cell production becomes even more abnormal. This is why healthcare providers monitor patients with myelofibrosis closely throughout their disease course.