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Myeloproliferative Neoplasms

  • A group of blood cancers in which the bone marrow produces too many red blood cells, white blood cells, or platelets
  • Symptoms include headache, fever, fatigue, anemia, bruising or bleeding easily
  • Treatment includes therapeutic phlebotomy, cytoreductive therapy, aspirin, chemotherapy, immunotherapy, targeted therapy, stem cell transplant
  • Involves Yale Cancer Center, hematology program, pediatric hematology & oncology program

Myeloproliferative Neoplasms


Myeloproliferative neoplasm is a term used to describe a group of blood cancers that are connected by their cause—genetic aberrations to the cells in the bone marrow, which produce excessive numbers of myeloid blood cells (red cells, white cells, and/or platelets) as a result. They are sometimes slow-growing cancers, but in certain cases, they may progress to acute myeloid leukemia—a rapid-progressing cancer—especially if they are not treated.

About 20,000 Americans are diagnosed with myeloproliferative neoplasms annually. They’re more common among people who are in their 50s, 60s or older.

A variety of treatments, ranging from watchful waiting to stem cell transplants, may help people who have been diagnosed with myeloproliferative neoplasms. Treatment may help alleviate symptoms, reduce the risk of complications, and slow or stop the progression of the disease.

“Significant progress has been made in the last 20 years, allowing an ‘operational’ or ‘functional’ cure of most patients with chronic myeloid leukemia [CML], a type of myeloproliferative neoplasm previously associated with a median life expectancy of about five years,” says Yale Medicine hematologist and oncologist Nikolai Podoltsev, MD, PhD.

What are myeloproliferative neoplasms?

Normally, the blood stem cells that are produced within the bone marrow are responsible for making red blood cells, white blood cells, and platelets—all of which circulate throughout the body. In people with myeloproliferative neoplasms, acquired genetic abnormalities allow the blood stem cells in the bone marrow to create too many blood cells, leading to the uncontrolled reproduction of red blood cells, white blood cells, or platelets.

There are different types of myeloproliferative neoplasms. Classical myeloproliferative neoplasms are Philadelphia chromosome negative, meaning the Philadelphia chromosome—an abnormal chromosome—isn’t present.

Five classical myeloproliferative neoplasms are:

  • Polycythemia vera, the most commonly diagnosed of the myeloproliferative neoplasms. It often causes an increased production of red blood cells, white blood cells, and platelets, which may cause the blood to thicken and more likely to clot.
  • Essential thrombocythemia, which is the most slow-growing of the myeloproliferative neoplasms. It causes the bone marrow to produce too many platelets; red or white blood cells remain unaffected.
  • Primary myelofibrosis, which the rarest type of myeloproliferative neoplasm and also the most aggressive. People with the condition produce more blood cells than usual, but the blood cells don’t mature properly. Primary myelofibrosis also causes scarring of the bone marrow, which prevents it from producing blood cells. This leads to blood being produced in the spleen and/or liver instead.
  • Chronic neutrophilic leukemia and chronic eosinophilic leukemia, which are less common Philadelphia chromosome negative myeloproliferative neoplasms that cause too many white blood cells to be produced. They may also advance to acute leukemia.

In addition, Philadelphia chromosome positive chronic myeloid leukemia is another type of myeloproliferative neoplasm. Unlike classical types of the disease, the Philadelphia chromosome is present.  

Chronic myeloid leukemia, which is a slow-growing myeloproliferative neoplasm, may develop into acute leukemia if left untreated. People with this disease produce more blood cells than usual.

What causes myeloproliferative neoplasms?

Myeloproliferative neoplasms are caused by acquired genetic aberrations that usually arise during a person’s lifetime, rather than being passed along from one generation to the next. However, in rare instances, predisposition to genetic mutations may be inherited, and certain types of this cancer may infrequently run in families.

The genetic mutations that arise activate enzymes that turn on “switches,” which allow blood cells to multiply uncontrollably. People with “classical” myeloproliferative neoplasms often have genetic mutations to their JAK2, MPL, or CALR genes. Patient’s with CML have a chromosome abnormality that produces a new gene called BCR-ABL (Philadelphia chromosome), which also leads to the uncontrolled production of blood cells.

What are the symptoms of myeloproliferative neoplasms?

Sometimes, people with myeloproliferative neoplasms don’t experience any discomfort or other symptoms. In other cases, people who have myeloproliferative neoplasms may experience symptoms such as:

  • Headaches
  • Fever
  • Fatigue
  • Anemia
  • Bruising or bleeding easily
  • A new diagnosis of von Willebrand disease, a bleeding disorder
  • Blood clots in the veins or arteries, often causing pain or swelling at the site
  • Bone pain
  • A feeling of fullness in the abdomen
  • Enlargement or swelling of the spleen or liver
  • Unexpected weight loss
  • Itchy skin after showering or bathing
  • Redness, burning or tingling in the hands or feet
  • Night sweats

What are the risk factors for myeloproliferative neoplasms?

People who may be at increased risk of myeloproliferative neoplasms include those who:

  • Are age 50 or older
  • Have a history of blood clots
  • Have been previously exposed to high doses of radiation, including radiation therapy

How are myeloproliferative neoplasms diagnosed?

Doctors can diagnose myeloproliferative neoplasms after a physical exam, asking about symptoms, taking a medical history, and performing blood and bone marrow tests that can confirm the presence or absence of this type of blood cancer.

For a medical history, doctors may ask about anything that has changed with the patient’s health recently, including fatigue, anemia, bleeding abnormalities, or pain.

During a physical exam, a doctor may check for swollen or painful areas in the abdomen or legs, and other findings.

Doctors may use a number of tests to diagnose myeloproliferative neoplasms, such as:

  • Blood tests, which can determine whether there are too many red blood cells, white blood cells, or platelets present; whether blood cells have abnormalities; and whether genetic abnormalities are present in the blood cells
  • Bone marrow aspiration and biopsy, which can look for the presence of abnormalities in the bone marrow cells that are removed during the biopsy
  • Chromosome testing, which checks to see if any abnormalities exist in the chromosomes present in the blood or bone marrow
  • Molecular testing, which looks for the presence of gene mutations that may help to confirm the diagnosis of a myeloproliferative neoplasm

Additionally, people with a suspected diagnosis of polycythemia vera may have a serum erythropoietin level test. This hormone (erythropoietin) is usually low among polycythemia vera patients.

People with chronic myeloid leukemia may be diagnosed after receiving tests called fluorescence in situ hybridization (FISH) or molecular testing with reverse transcription–polymerase chain reaction test (RT–PCR), which look for changes or abnormalities in genes or chromosomes and detect BCR-ABL translocation (Philadelphia chromosome), which is monitored during the course of this disease by blood testing every 3 months.

How are myeloproliferative neoplasms treated?

A variety of treatments are available for myeloproliferative neoplasms. The type of treatment depends on the type of myeloproliferative neoplasm, how aggressive the condition is, the patient’s overall health, and other individualized factors.

Patients with classical myeloproliferative neoplasms, including polycythemia vera and essential thrombocythemia, are at risk of blood clots in the arteries and veins, which is the major complication of these chronic malignancies. Treatment of these conditions aims to prevent blood clots and improve symptoms associated with these diseases.

Patients with essential thrombocythemia and polycythemia vera have a more chronic disease course, but some patients with myelofibrosis have more aggressive illness requiring a treatment approach, such as allogeneic stem cell transplant, aimed at not only improvement of symptoms and low blood counts associated with the disease, but also survival.

Most patients with chronic myeloid leukemia can achieve an ‘operational’ cure with the use of tyrosine kinase inhibitors (TKIs), taken in pill form. If taken every day, TKIs can lead to normal blood counts and prevent progression to more aggressive forms of the disease. Some patients may have a “deep molecular response,” meaning the Philadelphia chromosome becomes undetectable on a test called polymerase chain reaction (PCR). These patients may discontinue the TKI pill after a few years and will remain in remission without needing additional treatment, thereby achieving a ‘functional’ cure.

Certain treatments may be used to remove or normalize the excess blood cells that have been produced:

  • For patients with too many red blood cells, for example, treatment may involve periodically removing blood from a vein. This treatment, known as therapeutic phlebotomy, can reduce the risk of the formation of blood clots.
  • Cytoreductive therapy with hydroxyurea, interferon, or ruxolitinib can be used for patients with polycythemia vera and essential thrombocythemia to lower the risk of blood clotting. These cytoreductive therapies reduce the level of blood cells in people with these diseases. Anagrelide, which is also a cytoreductive drug, can also be used for those with essential thrombocythemia.
  • Low-dose aspirin may be used to reduce the risk of blood clotting and improve symptoms in patients with polycythemia vera and essential thrombocythemia.

People with myeloproliferative neoplasms may also receive standard cancer treatments, including:

  • Chemotherapy, which works to stop cancer cells from growing uncontrollably
  • Immunotherapy, such as interferon, which helps to boost the body’s immune system to better fight the cancer
  • Targeted therapies, which are medications designed to destroy specific cancer cells without harming healthy cells; TKIs such as imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib are often given to people with CML and ruxolitinib is given to patients with classical myeloproliferative neoplasms
  • Stem cell transplants combined with high-dose chemotherapy, which may encourage the growth of healthy blood cells; after abnormal blood cells are destroyed by high-dose chemotherapy, stem cells (whether from a donor or from the patient, removed before chemotherapy) are given by infusion to kick-start the production of healthy blood cells. This intensive treatment is reserved for patients whose disease has progressed to more aggressive stages, including high-risk myelofibrosis and acute myeloid leukemia.

What is the outlook for people with myeloproliferative neoplasms?

People with myeloproliferative neoplasms have varied experiences, depending upon their age, overall health, and type of condition they have. When myeloproliferative neoplasms advance to acute myeloid leukemia, people may have a poorer prognosis.

What makes Yale Medicine's approach to myeloproliferative neoplasms unique?

“Hematology specialists at Yale Medicine provide care to patients with myeloproliferative neoplasms using the most novel approaches and treatment modalities, including clinical trial options available for patients with certain subtypes,” says Dr. Podoltsev. “These highly qualified physicians take care of many patients with myeloproliferative neoplasms and have significant experience in treating patients with these hematological malignancies. Members of the group participate on the writing panels of the National Comprehensive Cancer Network, the most definitive international consensus group responsible for establishing worldwide guidelines for the evaluation and treatment of myeloid malignancies, including myeloproliferative neoplasms. Our transplant group is the only one in Connecticut providing allogeneic stem cell transplantation to patients with myeloid malignancies, including aggressive forms of myeloproliferative neoplasms.”