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The Different Types of Myeloproliferative Neoplasms (MPN)

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March 13, 2023

Contributed by Dr. Muneeb Niazi, Medical Fellow at SurvivorNet.

Chronic myeloid leukemia (CML) is a type of blood cancer known as a myeloproliferative neoplasm (MPNs). There are several different types of blood cancer that fall under the MPN umbrella. These diseases are characterized by an over-proliferation of one of the components in the bone marrow. To understand how MPNs form, it’s important to first understand how the bone marrow normally functions.

The myeloid tissue, colloquially known as the bone marrow, produces life-sustaining components of the blood, including red blood cells, white blood cells, and platelets. Rarely, the bone marrow can rev up the production of one or more of these components. This overzealous production is a recipe for several blood cancers. Collectively, these are called myeloproliferative neoplasms (MPNs), a name that underlines the unchecked growth of the bone marrow cells.

“Myeloproliferative disease is an umbrella term, and it basically includes four different disease processes,” Dr. Eric Winer, clinical director of adult leukemia at Dana-Farber Cancer Institute, tells SurvivorNet. “…If you think about the bone marrow, in the bone marrow you make four different components: platelets, red blood cells, white blood cells, and the feeder layer which they all grow up on which is called the stroma. The over-proliferation, or the uncontrolled growth, of any one of those cells lead to these diseases.”

These MPNs include:

  • Polycythemia vera (PV)
  • Primary myelofibrosis
  • Essential thrombocythemia
  • Chronic myeloid leukemia (CML)
  • Chronic neutrophilic leukemia
  • Chronic eosinophilic leukemia

The first four are the most common MPNs. Common underlying features of these MPNs are genetic mutations, or alterations of the normal cell DNA, which permit the marrow cells to grow by leaps and bounds. These mutations are not hereditary. Instead, they are required during patients’ lifetimes for unknown reasons. The cells that are usually affected can generate one or more of the blood cells listed above.

Polycythemia Vera: A Cancer Of The Red Blood Cells

A relatively rare diagnosis overall, PV is one of the most common MPNs. It affects 22 out of every 100,000 people, with most patients diagnosed between the ages of 60 and 65 years. It is uncommon for younger people to develop PV.

RELATED: What Is Polycythemia Vera?


PV is the result of an overabundance of red blood cells. It is often accompanied by an increase in platelets. The exact cause is not fully understood but is likely related to mutations in the Janus kinase 2 (JAK2) gene. Such mutations are found in almost all PV patients. The specific role of this mutation in producing PV is the topic of current debate and ongoing research. It is important to note that most PV patients do not have any family history of the disease. The JAK2 driver mutation is acquired by the patient’s cells during their own lifetime. Less commonly, PV can run in families. This often happens in patients with Eastern European (Ashkenazi) Jewish ancestry.


As a patient’s red blood cells increase, the blood becomes thicker and more viscous. This severely reduces its ability to flow through the arteries and veins. An increased platelet count can lead to excessive clot formation within the blood vessels. Clotting is made worse by the thickened blood. Ironically, excessive clotting within the blood vessels is accompanied by an impaired ability to clot after external injuries. Together, these changes in the blood may present as:

  • Headaches
  • Dizziness
  • Blurry vision
  • Reddened skin
  • Tiredness
  • Burning sensation in the feet
  • Itchy skin after warm baths and showers
  • An enlarged spleen, called splenomegaly
  • Bleeding or easy bruising

While any combination of these symptoms can be present in PV patients, some patients may not have any notable symptoms.


PV is most often diagnosed by accident because of elevated RBCs noted on a routine blood draw such as a complete blood count (CBC). A CBC measures this volume in three different ways. Hematocrit, the first measure, is likely elevated beyond the normal 45% in PV patients. The second measure, hemoglobin, the molecule that carries oxygen within the RBCs, is also increased beyond its normal concentration of 150 grams/deciliter. The third measure is the RBC count, which in increased beyond the normal range. This range for men is 4.7 to 6.1 million cells per microliter (mcL) and for women 4.2 to 5.4 million cells/mcL). Additionally, a bone marrow biopsy may also be performed. It involves taking a sample of the bone marrow for analysis. This analysis can include genetic testing for the JAK2 mutation.

Primary Myelofibrosis: A Failing Bone Marrow

Primary myelofibrosis is the slow replacement of the prolific bone marrow by scar tissue or fibroblasts, which are cells that cannot produce blood products. Like PV, myelofibrosis is a rare disorder with an estimated 1.5 in 100,000 people afflicted. These patients also tend to be in their 60s and 70s.

RELATED: Understanding Primary Myelofibrosis


The specific cause of myelofibrosis is unknown. However, many patients carry JAK2 mutations, which are also found in PV patients. This is not required, and some patients may lack these mutations. Overall, there is an increase in chemicals that stimulate fibroblasts, cells that form connective tissues from collagen but not blood products. These cells slowly take over and replace the normal marrow cells, resulting in a decreased production of RBCs, WBCs, and platelets. This process is termed fibrosis.


Symptoms of myelofibrosis result from a lack of RBCs and platelets. Of note, as RBC production decreased within the bone marrow, the body compensates for it by increasing production in other areas of the body, such as the spleen and the liver, causing them to enlarge. Symptoms, thus, may include:

  • Anemia
  • Fatigue
  • Shortness of breath
  • Fever
  • Unintentional weight loss
  • An enlarged spleen (called splenomegaly)
  • An enlarged liver (called Hepatomegaly)
  • Abdominal fullness due to splenomegaly and/or hepatomegaly

Around 20% of people with this disorder may not have any symptoms.


A physical examination may hold the first clue of the disease. Splenomegaly and hepatomegaly can usually be felt by the patient and their doctor. This can prompt a blood test, which will reveal anemia (low hemoglobin) of varying degrees due to a dearth of RBCs. Often, these RBCs will also appear teardrop shaped under the microscope (normally, RBCs look like discs). Further testing can include a bone marrow biopsy, which may reveal extensive fibrosis within the marrow space. If the fibrosis is advanced, it may in fact be difficult to get a bone marrow sample, which could be another clue for the fibrotic process.

Essential Thrombocythemia: Too Many Platelets

Platelets are an essential part of the clotting process. However, too many platelets can result in clots in inappropriate locations and a lack of clotting where it is necessary, such as at the site of an injury. These are the hallmarks of essential thrombocythemia. Like the two MPNs mentioned before, this disorder is also rare, with 1 in 100,000 people affected, mostly aged 60 years or older.


Like PV and myelofibrosis, the exact cause of this disorder has not yet been determined. However, at least 90% of the cases are driven by genetic mutations acquired by the cells that produce platelets. JAK2 mutations are again implicated in the development of this disorder. Mutations in the CALR gene, which makes a protein (calreticulin) used by blood cells, and the myeloproliferative leukemia virus (MPL) gene, which can kickstart cancer development, may also contribute to the development of essential thrombocythemia. These genetic changes cause an overproduction of platelets.


Some common symptoms of the disorder include:

  • Headaches
  • Dizziness
  • Changes in vision
  • Numbness or tingling of the hands and feet
  • Redness and burning pain in the feet
  • Nosebleeds
  • Blood in stool
  • Bleeding from gums
  • Easy bruising

Because of inappropriate clotting, this condition can also cause severe, life-threatening symptoms, such as:

  • Mini strokes
  • Major strokes
  • Heart attacks


Usually, a blood count will show an abnormally increased number of platelets (greater than 450 platelets/mcL). When analyzed under a microscope, these platelets would usually be larger and have abnormal shapes. Genetic testing may be performed, revealing mutations in the JAK2, CALR, or MPL genes. Usually, benign causes of increased platelets and other MPNs must be ruled out before a diagnosis of thrombocythemia is made, since it is a diagnosis of exclusion.

Chronic Myeloid Leukemia: Ineffective White Blood Cells

CML is a cancer of the white blood cells (WBCs). Specifically, it affects cells called the myeloblasts, which are the parents of mature, infection-fighting WBCs. These cells undergo a genetic mutation due to the formation of the so-called Philadelphia (Ph) chromosome. This mutation allows the myeloblasts to spill immature WBCs into the blood, bone marrow, and spleen. These immature cells are not fit to fight off infections, and their presence in the body causes a host of problems seen in CML patients.

RELATED: Understanding Chronic Myeloid Leukemia (CML)


A CML cell acquires the Ph chromosome when two of its originally normal chromosomes, 9 and 22, break off and fuse together. This fusion brings certain genes together in an unnatural way. In the case of the Ph chromosome, the BCR and ABL1 genes are joined together, forming the abnormal BCR-ABL1 gene. This gene produces a mutant BCR-ABL1 tyrosine kinase, which is a protein that stimulates the CML cells to proliferate in great quantities. It is important to reiterate that this mutation is acquired, meaning that it is not something that a person is born with. The exact cause of this mutation is not known.


Most often, patients with CML do not have any symptoms. However, when symptoms do occur, they can include

  • Bone pain
  • Fatigue
  • Shortness of breath with minimal activity
  • Fever
  • Unintentional weight loss
  • Easy bleeding
  • Pain below the ribs due to splenomegaly
  • Night sweats
  • Easy bruising and bleeding

These symptoms occur because abnormal CML cells take up the place of normal blood-forming cells within the bone marrow. This lowers the RBCs in a patient’s blood, causing tiredness, and shortness of breath. A shortage of normal WBCs and platelets increase the risk of infection and bleeding respectively.


A CML diagnosis is usually suspected when a routine CBC detects an abnormally high number of WBCs. The CBC may also reveal fewer RBCs or platelets (platelets can be increased depending on the severity of the disease). A peripheral blood smear, which looks at blood cells under a microscope, will usually reveal immature WBCs in circulation. These cells are absent in the blood of healthy people.

A bone marrow biopsy and chromosomal (cytogenetic) analyses may also be performed, which can allow doctors to examine chromosomal abnormalities, such as the presence of Ph chromosomes. AFISH (Fluorescence In Situ Hybridization) or Quantitative Polymerase Chain Reaction (qPCR) can be used to detect the BCR-ABL1 gene with greater accuracy.

Key Takeaways

  • The most common myeloproliferative neoplasms (MPNs) include polycythemia vera, primary myelofibrosis, and essential thrombocythemia, and chronic myeloid leukemia. There are other, rarer forms of blood cancers.
  • Polycythemia Vera results in an increase in red blood cells within the blood, which makes it extremely viscous and difficult to flow.
  • Primary myelofibrosis is a slow replacement of the bone marrow with cells that cannot produce blood products, such as red or white blood cells, and platelets
  • Essential thrombocythemia signifies an increase in the number of platelets within the blood. This can cause excessive clotting within the body or, counterintuitively, excessive bleeding in response to injuries.
  • Chronic myeloid leukemia is a cancer of the white blood cells, resulting in the production of huge amounts of WBCs which take up space within the bone marrow and cannot fight infection when released into the blood.
  • These cancers usually carry similar symptoms. Oftentimes, they do not have symptoms and are detected through routine blood examinations.
  • Usually, special examinations, including chromosomal analyses, bone marrow biopsies, and genetic testing, are used to make a diagnosis of specific blood cancers.