Myelofibrosis (MF)

What is myelofibroris (MF)?

Myelofibrosis (MF) is a rare type of blood cancer characterized by the buildup of scar tissue, called “fibrosis,” in the bone marrow. As scar tissue increases, the bone marrow cannot make enough healthy blood cells. It is one of a related group of blood cancers known as “myeloproliferative neoplasms” (MPNs), in which bone marrow cells that produce blood cells develop and function abnormally.

When MF develops on its own (and not as the result of another bone marrow disease), it is called “primary myelofibrosis.” In other cases, another type of MPN, such as polycythemia vera (PV) or essential thrombocythemia (ET), can transform into MF. In these cases, it is known as “secondary MF,” which may also be referred to as “post-PV MF” or “post-ET MF.” Between 10 percent and 20 percent of all MF cases begin as either PV or ET.

 Some patients who have MF remain symptom-free for many years and do not require immediate treatment. All patients who have MF, however, need to be closely monitored.

The treatment goals for most patients with MF are to relieve symptoms, reduce an enlarged spleen, improve blood cell counts (i.e., reduce anemia), and reduce the risk of complications.

What should I do if I am diagnosed with MF?

• Talk with your doctor about your diagnostic tests and what the results mean.
• Talk with your doctor about all your treatment options, side effects, and the results you can expect from treatment.
• Ask your doctor whether a clinical trial may be a good treatment option for you.
• You should be treated by a hematologist-oncologist, who is a specialist who treats people who have MF or other types of blood cancer. Learn how to find a blood cancer specialist or treatment center.   

Learn more about communicating with your blood cancer specialist or find a list of suggested questions to ask your healthcare providers.

How does MF develop?

The cause of primary MF is not fully understood: It is a complex disease that may have many contributing factors.

Researchers believe that proteins known as Janus kinases (JAKs) are involved. These proteins send signals that affect the production of blood cells in the bone marrow. They also help control the number of red blood cells, white blood cells, and platelets. When JAKs are working normally, they help the body make the right number of blood cells. But when too many signals are sent by these proteins, it causes too many blood cells to be made in the bone marrow.

As the mutated overactive blood stem cell divides and makes copies of itself, it multiplies uncontrollably, creating many abnormal megakaryocytes in the bone marrow. (Megakaryocytes are the cells that produce platelets.) These abnormal megakaryocytes may change the environment of the bone marrow by releasing cytokines.

Some researchers believe this may cause inflammation and stimulate the buildup of fibrous tissue in the bone marrow. The web of fibers inside the bone marrow then becomes thick, like scar tissue. Over time, the fibrous tissue impairs the bone marrow’s ability to produce normal blood cells, leading to symptoms and complications. 

MF disease complications

As MF progresses, complications may arise. These include:

Blood clots  

People with MF have an increased risk of developing abnormal blood clots. When blood clots form in an artery, they can lead to a heart attack or a stroke. Deep vein thrombosis (DVT) occurs when a blood clot (thrombus) forms in one or more of the deep veins in the body, usually in the legs. This can cause pain, swelling and reddening in the affected area. If a blood clot from a deep vein breaks loose and travels to the lungs, it can become lodged in the lungs and block blood flow, causing a serious blockage called a “pulmonary embolism.” Symptoms of a pulmonary embolism include shortness of breath, chest pain and cough.

Bleeding

As MF progresses, the number of platelets may drop below normal levels. Insufficient platelets can lead to bleeding more easily than usual. Patients need to discuss bleeding concerns with their doctors when planning to have surgery or other medical procedures. 

Enlarged spleen

The spleen is an organ located on the left side of the upper abdomen, near the stomach and below the rib cage. It filters the blood, stores blood cells and destroys old blood cells. The spleen may become abnormally enlarged in people with MF because it is working harder to manage the increased number of blood cells. An enlarged spleen can cause discomfort or pain in the abdomen. When the spleen pushes up against the stomach, it may also cause a feeling of being full along with a decreased appetite.

Portal hypertension

Normally, blood flow from the spleen enters the liver through a large blood vessel called the portal vein. When the spleen is enlarged, increased blood flow through the portal vein can lead to high blood pressure in the vein. This can force excess blood into smaller veins in the stomach and esophagus, potentially causing the veins to rupture and bleed. Portal hypertension may also be caused by a blood clot that develops in the portal vein, which may obstruct the blood flow through it.

Extramedullary hematopoiesis

When the bone marrow is no longer able to make sufficient blood cells, other organs in the body such as the spleen may begin to produce blood cells. This often causes the spleen and liver to become enlarged. Extramedullary hematopoiesis may also lead to the creation of clumps or tumors of developing blood cells in other areas of the body, which may cause bleeding in the gastrointestinal (GI) system, coughing or spitting up blood, compression of the spinal cord, or seizures. 

Bone and joint pain

Myelofibrosis can cause hardening of the bone marrow and inflammation of the connective tissue that surrounds the bones, resulting in severe bone and joint pain and tenderness.

Gout

MF increases the body’s production of uric acid. When uric acid builds up, it forms crystals in the joints causing sharp pain, swollen joints, and inflammation.

Acute myeloid leukemia (AML)

In about 9 percent to 13 percent of patients MF will transform to AML, a type of blood and bone marrow cancer that progresses rapidly.

Find facts and statistics about MF and other blood cancers.

Source: Myeloproliferative Neoplasms. Reviewed by John Mascarenhas, MD.