Imagine your bone marrow working overtime, making too many blood cells and throwing your body off balance. That’s what happens in myeloproliferative neoplasms (MPNs), a rare group of blood cancers. The three main types of MPNs are primary myelofibrosis (MF or PMF), essential thrombocythemia (ET), and polycythemia vera (PV) — each affecting blood cells differently.

In primary MF, abnormal blood cells grow too quickly, and scar tissue forms in the bone marrow. In ET, too many platelets are produced, and in PV, it’s too many red blood cells. Some types of leukemia, including chronic myeloid leukemia (CML), are also considered types of MPN. MPNs are considered rare because fewer than 6 people in 100,000 are diagnosed each year in the United States.

Like other cancers, MPNs are caused by genetic mutations (changes) that allow cells to divide and grow uncontrollably. There are two main types of mutations, inherited and acquired.

Inherited mutations:

• Are passed down from parents to children
• Are in the DNA of all cells at birth
• Occur much less often

Acquired mutations:

• Happen throughout a person’s life
• Are caused by normal aging and exposure to carcinogens (something that can cause cancer), such as radiation, certain chemicals, smoking, and some viruses
• Are found in the DNA of some cells

Most cancer is the result of acquired mutations. The cause of the mutation is usually unknown. In a few cases, MPNs are related to inherited mutations, but MPNs are generally not considered to be inherited diseases. It’s still unclear why some people develop MPNs and others do not.

How Cells Transform Into Cancer

Normal cells divide in a regular, ordered fashion, forming new cells that are exact copies to replace old ones. Certain genes in each cell are responsible for telling cells when to divide and when to stop dividing. Other genes identify and fix problems in DNA that are copied incorrectly, or cause cells with bad DNA to self-destruct rather than keep multiplying.

If a genetic mutation causes one or more of these genes to turn off in some cells, the cells can divide at a faster rate without regulation or order, becoming more and more mutated. Mutations can build up over time, causing abnormal cells to grow even faster. When these disordered cells begin to invade nearby tissues or break off and migrate to other locations, they become cancerous.

Risk Factors for MPNs

Although science can find links between factors and diseases, these connections don’t always mean one causes the other. Many risk factors for MPNs have been identified and are being studied to understand their role in the disease.

Because genetic mutations cause MPNs, risk factors for MPNs include anything that can encourage mutations.

Age

Mutations in DNA happen naturally and build up as we get older. Researchers believe that in tissues that divide quickly, like blood stem cells, thousands of mutations can build up by the time you’re 60 years old. However, cancer only develops in a small percentage of people.

The three classic types of MPNs are generally diagnosed in people over 50 years of age. PV and ET tend to be diagnosed around 60 years of age. Although increased age is a risk factor in ET, 20 percent of cases develop in people under age 40. Primary MF is most commonly diagnosed in people older than 50.

The American Cancer Society notes that the risk for CML goes up with age. Chronic neutrophilic leukemia (CNL) doesn’t have any known risk factors. The median age for CNL diagnosis is 66 years, and people from ages 15 to 86 have been diagnosed with the condition.

Inherited Factors

Although MPNs aren’t considered inherited diseases, it’s possible for more than one person in a family to have an MPN. In rare cases, MF and PV have been found to run in families.

According to the Leukemia and Lymphoma Society, PV is more prevalent among Jewish people of Eastern European descent than in those with other backgrounds.

Gender is a minor risk factor in some MPNs. According to MPN Research Foundation, women are 1.5 times more likely to develop ET than men. CML is slightly more common in men than in women.

Environmental Factors

Anything that raises the risk of acquired genetic mutations also raises the risk of developing MPNs and other types of cancer. Several carcinogens have been identified as contributing to the risk of MPN.

Radiation

Exposure to radiation increases the risk of developing certain types of MPNs. Everyone is exposed to low levels of radiation from natural sources, such as the sky and the earth. Many building materials naturally contain low levels of radiation. Some people are exposed to naturally occurring radon gas in their homes. Human-made sources of radiation include X-rays, computerized tomography (CT) or positron emission tomography (PET) scans, and radiation therapy.

Although the levels of radiation most people are exposed to are low, the effects of radiation can accumulate over time and gradually cause mutations that sometimes lead to MPNs. People in jobs that expose them to higher levels of radiation — such as workers in nuclear power plants — may have a higher risk of developing CML or primary MF.

Chemicals

People who work with carcinogenic chemicals, such as benzene and toluene, may be more likely to develop primary MF.

Smoking

Studies from the journal HemaSphere suggest that smoking a pack of cigarettes per day for 20 or more years may be a risk factor for PV in women, specifically.

Acquired Mutations Associated With MPNs

Scientists have identified several acquired genetic mutations in blood stem cells that often play a role in developing MPNs. The genetic mutations usually in the three most common MPNs include the JAK2, CALR, and MPL gene markers. Mutations that disrupt the function of these genes can contribute to the uncontrolled growth of blood stem cells. Knowing which mutations are in cancer cells helps doctors recommend effective MPN treatment options.

According to the National Cancer Institute’s Dictionary of Cancer Terms:

• JAK2 is a gene that makes a protein called Janus kinase 2, which sends signals in cells that promote cell growth.
• CALR is a gene that makes a protein called calreticulin, which helps control the amount of calcium stored in cells.
• MPL is a gene that makes a protein called the thrombopoietin receptor, which helps control the number of blood cells made in the bone marrow.
• Colony-stimulating factor 3 receptor (CSF3R) is a gene that controls the growth and function of certain white blood cells.

Polycythemia Vera

In roughly 95 percent of people with PV, cancer cells have a JAK2 gene mutation. Specifically, the JAK2V617F gene is found in blood-forming cells.

Essential Thrombocythemia

In cases of ET, there may be mutations of JAK2, CALR, or MPL genes. About 60 percent of ET cases involve a JAK2 gene mutation and roughly 33 percent involve an MPL mutation.

Primary Myelofibrosis

Between 50 percent and 60 percent of people with MF test positive for a JAK2 gene mutation. Estimates of those with MF who have the acquired genetic mutation CALR range from 3 percent to 24 percent. In addition, estimates range from 5 percent to 33 percent for the mutation of the MPL gene.

Chronic Myeloid Leukemia

In most cases of CML, cancer cells have a genetic abnormality called the Philadelphia chromosome (Ph+). This genetic change, known as BCR-ABL, was named after the city where it was discovered. It happens when part of chromosome 22 swaps places with part of chromosome 9. In rare cases of CML, there may be a different mutation in the CSF3R gene.

Chronic Neutrophilic Leukemia

Mutations in the CSF3R gene are common in people with CNL.

Chronic Eosinophilic Leukemia

Chronic eosinophilic leukemia has not been associated with a specific chromosome or genetic abnormality, but on rare occasions may be linked to an acquired mutation.

Talk to Your Doctor

MPNs are rare blood cancers caused by genetic mutations that can develop over time because of factors like aging, radiation exposure, and certain chemicals. Some mutations are inherited, but most develop during a person’s life. Knowing the risk factors, such as age, family history, and environmental exposure, can help with early diagnosis and management.

If you or a loved one has been diagnosed with an MPN, it’s important to talk to a health care provider to learn about treatment options based on specific genetic changes.

Find Your Team

On myMPNteam, the social network for people with myeloproliferative neoplasms and their loved ones, more than 4,000 members come together to ask questions, give advice, and share their stories with others who understand life with MPNs.

Have you or a loved one been diagnosed with MPNs? Are you looking for support and information on managing life with the condition? Share your experience in the comments below, or start a conversation by posting on your Activities page.