Polycythemia vera causes and risk factors
Fact-checked by Polycythemia vera (PV) is a rare, slow-growing blood cancer that causes your body to make too many blood cells. It most commonly leads to an increase in red blood cells, but it can also raise the number of platelets, which help your blood clot, and certain white blood cells.
If you or someone you care about has been diagnosed with PV, knowing its causes can help you better understand why the condition developed. It can also help you understand how your healthcare team, or your loved one’s doctor, chooses the most appropriate treatment. Still, while researchers know what drives PV, they don’t fully understand why some people develop the disease and others do not.
What causes PV?
Like other cancers, PV develops because of genetic changes, or mutations, in certain cells, which cause them to grow and divide uncontrollably.
In PV, these mutations occur in blood stem cells found in your bone marrow, the soft, spongy tissue inside your bones where blood cells are formed. These cells normally develop into red blood cells, white blood cells, and platelets throughout your life to replace older or damaged blood cells.
However, if one of these stem cells acquires a disease-causing mutation, it begins producing too many red blood cells. Over time, this buildup of extra blood cells can thicken your blood and make you more prone to develop blot clots, which can lead to severe complications such as stroke.
The role of JAK2 mutations in PV
Nearly all people with PV have a mutation in a gene called JAK2. About 95% of those with the disease have a key change known as the V617F mutation, and most others have mutations in a different part of the gene known as exon 12.
The JAK2 gene provides instructions for making a protein with the same name, which helps regulate when blood-forming cells make new blood cells.
PV mutations involving JAK2 cause this signaling pathway to become overactive, and to send constant growth signals. As a result, stem cells continue producing red blood cells, and sometimes platelets and certain white blood cells, even when your body does not need them. This uncontrolled blood cell production is the hallmark of PV.
Are PV mutations inherited?
PV is a rare condition that affects about 50 people per 100,000. If you’ve wondered “Is PV inherited?” the answer is usually no.
Most people with PV do not inherit the condition from a parent. Instead, the JAK2 mutations that cause PV are acquired. This means they develop during your lifetime in your bone marrow cells and cannot be passed on to your children.
Nevertheless, researchers have found that having a family history of PV may slightly increase your risk of developing it. This is because there are certain genetic factors that do not directly cause the disease but may increase your chances of developing PV. Inheriting those genetic variations may make some people more likely to develop a JAK2 mutation later in life.
Risk factors for PV
Although anyone can develop PV, certain factors may make it more likely.
PV is diagnosed most often in people older than 65, although about 10% receive a diagnosis before reaching their 40s. Some studies also suggest PV is slightly more common in white people and people of European ancestry. Also, while PV affects both men and women, men are somewhat more likely to develop the disease. Â
Researchers are continuing to study other possible PV risk factors. Some chronic health conditions, including diabetes, high blood pressure, high cholesterol, and obesity, may be associated with an increased risk of developing PV. People who smoke also appear to have a slightly higher risk.Â
Recent research suggests that chronic inflammation also may contribute to the development of JAK2 mutations. In addition, genetic mutations other than JAK2 may influence your prognosis, or the expected course of the disease, after you are diagnosed.
PV vs. secondary polycythemia
PV develops because of acquired genetic mutations in blood-forming cells, most often involving the JAK2 gene. Secondary polycythemia, by contrast, occurs when your body produces too much erythropoietin (EPO), a hormone made primarily by the kidneys that stimulates red blood cell production.
Although they share some symptoms, PV and secondary polycythemia are different conditions. Both can cause an increase in red blood cells, but they develop for different reasons and are treated differently.Â
Because secondary polycythemia is much more common than PV, it should be ruled out before a person can be diagnosed with PV.
Secondary polycythemia can develop for several reasons, including:
- Living at high altitudes: Lower oxygen levels can stimulate your body to produce more EPO, increasing red blood cell production.
- Lifestyle factors that reduce oxygen levels: Long-term carbon monoxide exposure, cigarette smoking, or hookah smoking can lower the amount of oxygen in your blood and trigger increased EPO production.
- Chronic conditions that affect oxygen levels: Conditions such as lung disease, obstructive sleep apnea, or congenital heart defects that reduce oxygen levels can also tell your body to create more red blood cells, leading to secondary polycythemia.
- Certain cancers: Some tumors in the central nervous system, kidneys, and liver can increase EPO production.
- Kidney transplant: Some people who receive a kidney transplant produce more EPO than normal, which can contribute to secondary polycythemia.
- Certain medications: Synthetic EPO, sodium-glucose cotransporter-2 (SGLT2) inhibitors used to treat diabetes, and androgen supplements can all raise EPO levels.
- Rare inherited genetic mutations: In uncommon cases, inherited mutations affecting the EPO pathway can lead to secondary polycythemia.
Why finding the cause matters for diagnosis and care
Determining the underlying PV causes is an important step in getting the right diagnosis and treatment. Although PV and secondary polycythemia can appear similar, they have different underlying causes and require different approaches to care.
If you have PV, treatment focuses on lowering the number of blood cells your body produces and reducing your risk of serious complications, such as blood clots. If you have secondary polycythemia, treatment is usually directed at the condition causing your body to produce too many red blood cells.
Understanding the cause of your condition can help your healthcare team recommend the most appropriate treatment plan. It can also help you to monitor your health over time and lower your risk of long-term complications.
If you have questions about your diagnosis or treatment, talk with your healthcare provider. Your healthcare team can explain what is causing your condition and what it means for your care.
Rare Cancer News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
