Understanding the causes of polycythemia vera

Table of contents

• Understanding the causes of polycythemia vera
• What is polycythemia vera?
• The primary cause: JAK2 gene mutation
• Risk factors for developing PV
• Complications linked to PV causes
• What causes secondary polycythemia?
• Expert perspective on understanding causes
• FAQs
• Blood Cancer United cancer research impact
• Conclusion
• Sources

If you or someone you care about has been diagnosed with polycythemia vera (PV), understanding why it develops is the first step toward empowered, proactive care.

PV is a rare blood cancer that belongs to the family of myeloproliferative neoplasms (MPNs). These are conditions in which the bone marrow produces too many blood cells. Extra cells thicken the blood and may strain the heart or spark clots. 

You deserve clear answers when suspicious blood counts raise concern. So, understanding why PV arises is important for early detection, tailored treatment, and peace of mind.

What is polycythemia vera?

Polycythemia simply means “many cells.” In polycythemia vera, the surplus involves red blood cells—often white cells and platelets as well. Unlike other conditions that cause the body to make extra red blood cells in response to low oxygen—such as smoking, lung disease, or living at high altitude—polycythemia vera starts within the bone marrow itself. 

This overproduction happens because the bone marrow keeps making blood cells even when the body doesn’t need them. Unlike a normal response to low oxygen, it continues on its own, thickening the blood and putting extra strain on the heart and blood vessels. 

Because the excess is unprovoked, routine fixes such as extra oxygen do not correct it. PV sits apart from other marrow disorders because it almost always traces back to one pivotal genetic change: the JAK2 mutation. (Blood Cancer United, 2025).

The primary cause: JAK2 gene mutation

Researchers have found that about 95 percent of people with PV have a key mutation in a gene called JAK2, which controls how the bone marrow makes blood cells. The most common form of this change—known as the V617F mutation—switches on a growth signal called the JAK-STAT pathway, causing the marrow to keep producing red blood cells even when the body doesn’t need them. 

This discovery helps explain why PV develops and how doctors can target it. By understanding the JAK2 mutation, researchers can design treatments that calm this overactive signal, helping bring blood production back into balance. 

While the V617F mutation is the most common change, found in nearly all people with PV, the exon 12 mutation affects only a small percentage (about 4 percent). It tends to appear in PV patients who lack the V617F mutation—yet both trigger the same overactive signal in the bone marrow. (Blood Cancer United, 2025). 

Scientists supported by Blood Cancer United are also studying other genes, such as TET2 and ASXL1, which help regulate how blood cells grow and mature. Changes in these genes don’t cause PV on their own but may influence how the disease develops or responds to treatment. (Barbui et al. 2015). 

Together, these discoveries give researchers a clearer picture of how PV begins and evolves. Understanding the different genetic pathways involved helps scientists refine diagnostic tests and develop therapies that target the root cause rather than just the symptoms. 

Still, the main gene mutation causing polycythemia vera is in JAK2. This mutation primarily drives the increase in red blood cell count that characterizes PV (Blood Cancer United, 2025). Because this mistake sits within the stem cell, it is not contagious and rarely passes to children, yet it defines what causes polycythemia vera for almost every individual diagnosed.

Risk factors for developing PV

Certain life circumstances appear to raise the odds of acquiring the JAK2 mutation, or of the mutant clone expanding: 

• Age: In general, myeloproliferative neoplasms are rare in anyone under 40, while the majority of cases occur in people 65 and older (Blood Cancer United, 2025).
• Sex: Men and women can develop PV, but it’s slightly more common in men (Nagalla 2014). 
• Family history: Having a first-degree relative with PV or another MPN slightly increases risk, suggesting shared genetic susceptibility rather than direct inheritance (Blood Cancer United, 2025). 
• Environmental exposures: High doses of radiation or exposure to benzene have been connected to certain mutations in the bone marrow. Routine X-rays and other imaging tests usually involve only tiny amounts of radiation. 
• Underlying health conditions: Obesity, smoking, or untreated sleep apnea does not cause PV. They increase baseline red-cell mass and can mask or mimic early disease (NCCN 2024). 

Understanding these factors can prompt earlier blood tests and help clinicians distinguish PV from conditions that raise red blood cells indirectly.

Complications linked to PV causes

The same overproduction that defines polycythemia vera also explains its complications. Thickened blood moves sluggishly, allowing clots to form. 

Persistent elevation of red cells and platelets heightens the risk of blood clots.These clots can show up as deep vein thrombosis, pulmonary embolism, heart attacks, or strokes. 

Over time, the abnormal cells in your bone marrow can cause scarring or even turn into a type of acute leukemia called acute myeloid leukemia (AML) (Blood Cancer United, 2025). Although progression rates are low (2–5 percent for AML), it’s essential to keep a close eye on your blood counts and follow your doctor’s recommendations to catch any issues early.

What is secondary polycythemia?

Secondary polycythemia is a rare disease that happens when the body creates too many red blood cells. It is different from polycythemia vera due to the cause of disease. While PV is due to the JAK2 mutation, in secondary polycythemia, your body has high levels of erythropoietin (a hormone) which tells your body to create more red blood cells. Common reasons for this to happen include:

• Cardiac (heart) disease
• Pulmonary (lung) disease
• Smoking
• Kidney or liver abnormalities, including cancers
• Genetics
• Obesity
• Living at high altitudes
• Chronic hypoxia from lung disease or congenital heart defects
• Obstructive sleep apnea that deprives tissues of oxygen overnight
• Erythropoietin-secreting tumors of the kidney or liver

It is very important to find out the cause of your high red blood cell count. If your doctor is concerned about polycythemia vera, a bone marrow biopsy will be requested. Getting a second opinion at a larger cancer center is also recommended.

Expert perspective on understanding causes

Hematologists look for three key signs when diagnosing PV: 

1. Consistently high hematocrit or hemoglobin levels 
2. Low erythropoietin levels 
3. The presence of a JAK2 mutation 

These three findings work together to confirm whether the bone marrow is making blood cells on its own rather than in response to another condition. 

When any element is unclear, a bone marrow biopsy provides definitive evidence of a marrow disorder (Barbui et al. 2015). Continued research by Blood Cancer United aims to refine these criteria and uncover additional genetic clues that could predict progression or response to therapy.

FAQs

What is the main cause of polycythemia vera? 

An acquired mutation in the JAK2 gene, most often the V617F change, drives uncontrolled production of blood cells. 

Is polycythemia vera hereditary? 

PV itself is not passed down, but close relatives have a slightly higher incidence, suggesting shared predispositions. 

Can lifestyle or environment cause PV? 

No single behavior triggers PV, although long-term radiation or benzene exposure may raise the risk. Routine X-rays and other imaging tests usually involve only tiny amounts of radiation. Healthy habits remain important for overall heart and vascular health. 

Does every person with PV have a JAK2 mutation? 

Most people do—around 95 percent have the JAK2 V617F mutation, while another four percent have the JAK2 exon 12 mutation. (Blood Cancer United, 2025). 

What tests confirm PV? 

A complete blood test for counts, serum erythropoietin, a molecular assay for JAK2, and often a bone marrow biopsy establish the diagnosis.

Blood Cancer United cancer research impact

Blood Cancer United is here to support anyone affected by any blood cancer—including polycythemia vera. Our work focuses on: 

• Driving research breakthroughs: As the largest nonprofit funder of blood cancer science, Blood Cancer United backs investigations that span every myeloproliferative neoplasm—including the landmark studies that pinpointed the JAK2 mutation—and continues to refine PV‑specific therapies such as JAK inhibitors.
• Delivering hands‑on support: Whether you need help locating a clinical trial for a new PV treatment, free educational booklets such as the MPN Booklet, guidance on insurance coverage for regular phlebotomies, or a sympathetic ear to discuss lab results, our blood cancer Information Specialists connect you with practical and emotional resources the moment you ask. 
• Championing patient‑first policies: Through the Office of Public Policy, Blood Cancer United pushes for legislation that speeds innovative PV drugs through approval and makes healthcare more accessible. 
• Spreading knowledge: From the comprehensive MPN booklet to live educational programs, Blood Cancer United translates complex science into clear, actionable information so you and your family can recognize symptoms early, understand test results, and make confident treatment decisions. 

Every donation helps advance discovery, smooth the care pathway, and empower people living with polycythemia vera and other blood cancers to thrive. If this overview clarifies the cause of polycythemia vera for you or someone you love, consider donating today.

Conclusion

Understanding what causes polycythemia vera—specifically the role of the JAK2 mutation and how it impacts your body—equips you to partner with your care team, monitor counts diligently, and act swiftly at the first sign of a heart attack or stroke. It also clarifies why treatments such as phlebotomy, aspirin, or JAK inhibitors work to counteract the excess blood circulating in your system. 

Each person's situation is unique, and we are here to help you ask the appropriate questions, identify the best treatment options, and, most importantly, enhance your quality of life. Please contact us if you or a loved one has been diagnosed with PV so we can provide professional resources and empathetic guidance. Together we turn understanding into action—and action into hope. 

For comprehensive information on diagnosis and treatment, visit our polycythemia vera resource hub. Always discuss personal medical decisions with your healthcare team. 

About the author: Dr. Ali is a medical journalist and copywriter.

Sources

Blood Cancer United. Facts 2024-2025. Updated Data on Blood Cancers. Published September 2025. Accessed March 3, 2026. BloodCancerUnited.org/resources/educational-resources/publications/booklet/facts-updated-data-blood-cancers.

Blood Cancer United. 2025. “Myeloproliferative Neoplasms, Polycythemia Vera, Essential Thrombocythemia and Myelofibrosis.” Myeloproliferative Neoplasms. https://bloodcancerunited.org/blood-cancer/myeloproliferative-neoplasms-mpns/polycythemia-vera-pv. 

Barbui et al. “The 2016 WHO Classification and Diagnostic Criteria for Myeloproliferative Neoplasms: Document Summary and In-depth Discussion.” Blood Cancer Journal 8, no. 2 (February 9, 2018). https://doi.org/10.1038/s41408-018-0054-y. 

Nagalla, Srikanth. “Polycythemia Vera: Practice Essentials, Pathophysiology, Etiology.” Medscape, December 14, 2014. https://emedicine.medscape.com/article/205114-overview#a6. 

NCCN. “NCCN Guidelines for Patients: Myeloproliferative Neoplasms, 2024,” 2024. https://www.nccn.org/patients/guidelines/content/PDF/mpn-patient.pdf.