Myeloproliferative neoplasms

Facts

Myeloproliferative neoplasms (MPN) are a group of diseases that affect blood-cell formation. In all forms of MPN, a bone marrow problem leads to increased levels of blood cells circulating in the bloodstream.

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets.

“Myelo” refers to bone marrow, which is the body’s blood-cell factory.

“Proliferative” refers to the rapid growth and production of cells.

“Myeloproliferative” means increased growth and production of bone marrow and blood cells.

“Neoplasm” means an abnormal growth of cells. A neoplasm can be either benign (noncancerous) or malignant (cancerous). In MPN, the neoplasm starts out benign; over time it may turn into malignant disease.

To understand more about MPN, it’s important to understand some basics about how blood cells normally form.

Benign Not cancer. Benign tumors may grow larger but do not spread to other parts of the body. Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Nonmalignant Not cancer. Nonmalignant tumors may grow larger but do not spread to other parts of the body. Also called benign.

Healthy blood-cell formation

In a healthy person, the stem cells in the bone marrow make daughter cells. The daughter cells go through several stages of development within the marrow. Eventually they mature into red blood cells (RBCs), white blood cells (WBCs), or platelets. These get released from the marrow to circulate in the bloodstream.

The circulating cells perform important functions.

RBCs carry oxygen throughout the body.
WBCs fight infection.
Platelets protect against easy bleeding by helping your blood to clot.

Blood-cell formation in MPN

In a person with MPN, stem cells in the bone marrow develop genetic defects (called acquired defects) that cause them to grow and survive abnormally. This results in unusually high numbers of blood cells in the bone marrow (hypercellular marrow) and in the bloodstream.

A high level of RBCs is called polycythemia.
A high level of WBCs is called leukocytosis.
A high level of platelets is called thrombocytosis.

High levels of blood cells cause some of the symptoms of MPN.

Sometimes in MPN, the abnormal stem cells cause scarring in the marrow, called myelofibrosis. Myelofibrosis may lead to low levels of blood cells, especially low levels of red blood cells (anemia).

In MPN, the abnormal stem cells can also grow in the spleen, causing the spleen to enlarge (splenomegaly), and in other sites outside the marrow, causing enlargement of other organs.

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Red blood cell A type of blood cell that carries oxygen in the body. Red blood cell A type of blood cell that carries oxygen in the body. Spleen An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells and destroys old blood cells. It is on the left side of the abdomen near the stomach. Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Types of MPN

There are several types of chronic MPN, based on the cells affected. The information about diagnosis and treatment in this section is mainly about the three classic types of MPN.

Polycythemia vera (PV), in which there are too many RBCs
Essential thrombocythemia (ET), in which there are too many platelets
Primary myelofibrosis (PMF), in which fibers and blasts (abnormal stem cells) build up in the bone marrow

Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

Other types of MPN

Chronic myeloid leukemia, in which there are too many WBCs
Chronic neutrophilic leukemia, in which there are too many white blood cells called neutrophils
Chronic eosinophilic leukemia, not otherwise specified, in which there are too many white blood cells called eosinophils (hypereosinophilia)
Mastocytosis, also called mast cell disease, in which there are too many mast cells, which are a type of immune system cell found in tissues, like skin and digestive organs, rather than in the bloodstream
Myeloproliferative neoplasms, unclassifiable—meaning your MPN does not fit into one of the other types
Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of the PDGFRA, PDGFRB, and FGFR1 genes

Some problems with blood-cell formation are not only myeloproliferative (having to do with overproduction of cells in the marrow) or only myelodysplastic (having to do with abnormal production of cells in the marrow). Instead, these problems have features of both MPN and myelodysplastic syndrome (MDS). They are described in the section about MDS subtypes.

Prognosis

The prognosis for people with myeloproliferative neoplasms (MPN) is relatively good, in general, with the appropriate treatment.

People with essential thrombocythemia typically have a normal lifespan. People with polycythemia vera (PV) or primary myelofibrosis (PMF) may have a shorter-than-normal life, living maybe more than 10 years from diagnosis with PV and possibly less time with PMF.

Many factors can affect the outlook for an individual, including their degree of myelofibrosis, the percentage of blasts (abnormal blood stem cells) in their blood and bone marrow, and any chromosome abnormalities they may have.

MPN can change over time, progressing from early chronic phases to accelerated phases. This can be followed either by burn-out phases (when the bone marrow is “burned out” and doesn’t make enough healthy blood cells) or by a blast crisis (when the disease resembles acute leukemia and there is an increase in the number of abnormal stem cells in your bone marrow or blood; this is a reason your doctor might recommend chemotherapy).

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Chemotherapy Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may be given alone or with other treatments. Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection, infusion or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy or biologic therapy. Chromosome Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. Prognosis A statement about the likely outcome of a disease in a patient. Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

Symptoms

Some people with myeloproliferative neoplasms (MPN) have no symptoms when their disease is diagnosed. But a routine blood test may show high levels of red blood cells, white blood cells, or platelets. Other people with MPN may have general symptoms, such as fever, night sweats, and weight loss. Each type of MPN may cause specific symptoms related to high blood counts.

Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Red blood cell A type of blood cell that carries oxygen in the body. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Polycythemia vera (PV) symptoms

Symptoms of PV, in which there are too many RBCs, may include the following:

A feeling of pressure or fullness below the ribs on the left side
Headaches
Double vision or seeing dark or blind spots that come and go
Itching all over the body, especially after being in warm or hot water
Reddened face that looks like a blush or sunburn
Weakness
Dizziness
Weight loss for no known reason

Red blood cell A type of blood cell that carries oxygen in the body. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Essential thrombocythemia (ET) symptoms

Symptoms of ET, in which there are too many platelets, may include the following:

Headaches
Stroke symptoms
Chest pains
In some cases, bleeding

Platelet A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets help form blood clots to slow or stop bleeding and to help wounds heal. A tiny, disc-shaped piece of a cell that is found in the blood and spleen. Platelets are pieces of very large cells in the bone marrow called megakaryocytes. They help form blood clots to slow or stop bleeding and to help wounds heal. Having too many or too few platelets, or having platelets that do not work as they should, can cause problems. Checking the number of platelets in the blood may help diagnose certain diseases or conditions. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Primary myelofibrosis (PMF) symptoms

Symptoms of PMF, in which fibers and blasts (abnormal stem cells) build up in the bone marrow, may include the following:

Weakness and fatigue from severe anemia
Abdominal pain and fullness from enlarged spleen and liver

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets. Spleen An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells and destroys old blood cells. It is on the left side of the abdomen near the stomach. Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Complications

A major complication of MPN is blood clots in the arteries, causing heart attacks and strokes, or in the veins, causing deep vein thrombosis and pulmonary emboli (clots that block the arteries that go from the heart to the lungs). Budd Chiari syndrome is a severe type of clot that involves the blood vessels leading to the liver. Blood clots can occur early, even before the diagnosis, and late in the disease.

Other complications may include the following:

Scarring of the bone marrow, called myelofibrosis. In PMF, this scarring can occur early on and be the main finding in the disease. In PV and ET, scarring can occur after many years of disease.
The transformation of MPN into acute leukemia.

Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets.

Diagnosis

To find out whether you have MPN, your doctor will first do a thorough physical exam and ask about your health history and any symptoms.

Next your doctor will perform a series of blood tests to tell whether any blood cells are abnormal and, if so, which ones. Common blood tests include the following:

Complete blood count (CBC): determines how many cells of each type are circulating in the bloodstream
Peripheral blood smear: looks at the appearance of the blood cells
Blood chemistry: looks for abnormalities in the blood, including certain enzymes or abnormal iron level

Peripheral blood smear A procedure in which a sample of blood is viewed under a microscope to count different circulating blood cells (such as red blood cells, white blood cells or platelets) and see whether they look normal. Symptom A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. A physical or mental problem that a person experiences that may indicate a disease or condition. Symptoms cannot be seen and do not show up on medical tests. Some examples of symptoms are headache, fatigue, nausea and pain.

Bone marrow aspiration and biopsy

For a definitive diagnosis, doctors generally need to perform a bone marrow aspiration and biopsy. A small area of skin over your lower back (pelvis) is cleaned and numbed. Then a marrow needle is used to withdraw bone marrow. If a biopsy is performed, the doctor uses a different needle to remove a small piece of marrow from your bone (a marrow core). In either case, the sample will be examined under a microscope to determine the presence and number of abnormal cells in your marrow and whether you have myelofibrosis.

Biopsy The removal of a sample of tissue or fluid that is examined to see whether cancer is present. This may be done with a large needle or through surgical removal of tissue or fluids. Bone marrow The soft, spongy material in the center of your bones that produces all your blood cells, such as white blood cells, red blood cells and platelets.

Cytogenetic analysis

In addition, doctors will perform cytogenetic analysis. This means your marrow cells will be set up in a culture dish to make them divide. This will allow us to see your chromosomes under a microscope and tell whether any are abnormal. Doctors use the number and type of chromosome abnormalities to help predict how your disease will progress and which types of treatment might be most effective. Your chromosomes contain your genes and can provide instructions for how your cells function.

Fluorescent in situ hybridization (FISH) is a specialized cytogenetic analysis. The fluorescent dyes used in this test attach to specific parts of certain chromosomes. More chromosomal abnormalities can be seen under a microscope using this technique than with the standard technique described above.

Molecular studies are very sensitive, specific tests for gene mutations associated with different myeloproliferative processes. Your doctors will use these tests to look for one or more of the following mutations:

BCR-ABL: a genetic joining of two genes found almost exclusively in chronic myeloid leukemia and rare cases of acute lymphoid leukemia
JAK2 V617F: a small mutation found in more than 90 percent of cases of PV and approximately 50 percent of cases of ET and PMF
MPL mutations: mutations in a protein that is found in some cases of ET
C-KIT D816V: a small mutation found in most cases of mastocytosis
FIP1L1-PDGFR: a genetic joining of two genes found in some cases of hypereosinophilia and associated with how the disease responds to treatment

Chromosome Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. Chromosome Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. Cytogenetic test The process of analyzing cells in a sample of tissue, blood, bone marrow or amniotic fluid to look for changes in chromosomes, including broken, missing, rearranged or extra chromosomes. The process of analyzing cells in a sample of tissue, blood, bone marrow or amniotic fluid to look for changes in chromosomes, including broken, missing, rearranged or extra chromosomes. Changes in certain chromosomes may be a sign of a genetic disease or condition or some types of cancer. Cytogenetic analysis may be used to help diagnose disease, plan treatment or find out how well treatment is working. Gene The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. Gene The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. Mutation Any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; mutations that occur in other types of cells are not inherited. Certain mutations may lead to cancer or other diseases. A mutation is sometimes called a variant.

Other tests

You may have flow cytometry (a computer analysis of cells) to tell how your disease is progressing.

Flow cytometry A laboratory method that measures the number of cells, the percentage of live cells and certain characteristics of cells in a sample of blood, bone marrow or other tissue. A laboratory method that measures the number of cells, the percentage of live cells and certain characteristics of cells (such as size and shape) in a sample of blood, bone marrow or other tissue. The presence of tumor markers, such as antigens, on the surface of the cells is also measured. The cells are stained with a light-sensitive dye, placed in a fluid and then passed one at a time through a beam of light. The measurements are based on how the stained cells react to the beam of light. Flow cytometry is used in basic research and to help diagnose and manage certain diseases, including cancer.

Risk factors

Doctors don’t know what causes the cellular changes that lead to MPN. Exposure to toxins, such as benzene, certain solvents or pesticides, and heavy metals, such as mercury or lead, may be involved in the development of genetic changes in stem cells. It is extremely difficult, if not impossible, to establish a clear cause-and-effect relationship between those exposures and the development of MPN.

MPN is seen in all age groups but is more common in middle age and older adults. PV is more common in men, and ET and PMF are more common in females. Very rarely, there can be clustering of cases in families that have an inherited genetic defect.

Stem cell A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

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