JAK2 is a signaling protein that sits inside blood-forming cells and helps relay growth messages from hormones and cytokines. [1] In a healthy system, these signals turn on and off as needed to regulate the production of blood cells, including white blood cells and platelets. [2]

In polycythemia vera (PV), a change in JAK2 keeps that growth signal “on,” which drives extra red blood cell production and, often, higher white blood cells or platelets as well. [3] This biology explains why blood can become thicker in PV and why symptoms, such as headaches, dizziness, or post-shower itching, correlate with blood counts. [4]

Understanding JAK2 doesn’t replace your clinical work-up, but it connects the “why” to the “what next.” It clarifies why your team sets a hematocrit goal, why ongoing monitoring is essential, and how treatment choices aim to reduce the risk of clotting while managing symptoms over time. [5]

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Most people with polycythemia vera carry a single, acquired mutation in the JAK2 gene, specifically the V617F mutation. A smaller group, typically a few percent, has exon 12 variants. Both switch the same growth pathway “on,” leading to overproduction of red blood cells; the difference is mainly which exact change in the gene is present. [6]

Two practical takeaways:

• Prevalence: The V617F mutation is found in ~95% of PV cases, while exon 12 changes account for the majority of the remaining cases. [7]
• How they can appear in labs: Patients with exon 12 variants may exhibit higher hemoglobin/hematocrit levels at diagnosis compared to those with V617F, but both reflect the same underlying biology: excess red blood cell production. [8]

Why this matters?

Knowing which JAK2 change is present helps your care team interpret patterns in your blood counts and symptoms.

Day-to-day management continues to focus on reducing the risk of clots and maintaining hematocrit levels within guideline targets, regardless of the JAK2 variant present.

In PV, a JAK2 change (most often V617F, sometimes exon 12) is one of the major diagnostic criteria. [9] It helps confirm that a myeloproliferative process is driving the excess production of blood cells. Here is a quick guide to put a JAK2-positive result into context and focus your discussion on what truly informs diagnosis and planning, without over-interpreting JAK2 blood work in isolation.

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Clinicians interpret a JAK2 mutation test together with other criteria. Current frameworks (International Consensus Classification [ICC], 2022) use three major criteria and one minor criterion. Diagnosis generally requires all three major criteria, or the first two major criteria + the minor criterion: [3]

• Major criterion 1— Elevated red blood cell levels: Hemoglobin ( >49% in men or >48% in women ) or hematocrit ( >16.5 g/dL in man or >16.0 g/dL in women) or red blood mass ( > 25%) above mean normal predicted value. This usually reflects excess red blood cell production.
• Major criterion 2 — Bone marrow biopsy showing increased blood-cell production: The bone marrow is more active than normal for a person’s age and is making too many of all three major blood cell types — red cells, white cells, and platelets. The platelet-forming cells (megakaryocytes) are increased in number but still look mature and normal in shape.

• Major criterion 3 — Presence of a JAK2 gene mutation: Usually V617F, less often exon 12 variants. This anchors PV biology.
• Minor criterion — Subnormal serum erythropoietin (EPO): A low EPO level supports the diagnosis when paired with the major criteria, helping distinguish PV from secondary causes of increased red blood cell mass.

What this means for you

A JAK2 mutation helps explain why your blood counts, especially your red blood cell count, and sometimes your white blood cell and platelet counts, are higher than normal. While hemoglobin/hematocrit, bone marrow features, and EPO show how those changes appear in your body. Some experts note that a “working diagnosis” can be made when JAK2 positivity accompanies hemoglobin / hematocrit above the mean normal predicted value, with bone marrow morphologic confirmation advised. [3] Keeping the hematocrit below 45% is then a common goal to reduce the risk of clotting. [15]

Tip to discuss at your next visit

Ask your care team how your latest hemoglobin/hematocrit, any bone marrow findings, JAK2 status, and EPO level fit together in their diagnostic framework.

In PV, JAK2-driven overproduction of red blood cells thickens the blood, increasing viscosity and, in turn, the risk of clots. Keeping hematocrit under guideline targets addresses this biology and is a core aim of polycythemia vera JAK2 management. [15]

The randomized Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) trial showed that patients treated to a hematocrit <45% had significantly fewer cardiovascular deaths and major thromboses than those kept between 45–50%. This finding established <45% as a standard goal used in practice. [15][16]

Current guideline summaries reflect: maintain Hct <45% for all patients, customizing the approach to achieve this (phlebotomy, low-dose aspirin, and, when appropriate, cytoreduction) to the overall risk and symptom burden. [16]

Tip to discuss at your next visit

Note your latest hematocrit and ask how it compares with your target, and which aspects of your plan (hydration habits, phlebotomy schedule, medications) are intended to keep your value within range.

Care plans aim to achieve two objectives: reducing the risk of clotting and managing symptoms while maintaining a hematocrit level within the target range. [3]

• First-line measures often include phlebotomy to reduce red blood cell mass and low-dose aspirin (when appropriate) to address the risk of clotting. [5]
• If counts or symptoms aren’t controlled, or if the risk is higher based on age or a history of clots, clinicians may add cytoreductive therapy. [5]
• Options commonly discussed include interferon formulations and hydroxyurea; JAK2 inhibitors may be considered in specific scenarios, guided by response and tolerance to these treatments.

What to clarify with your team:

• Which parts of my plan (phlebotomy schedule, aspirin, medications) are intended to maintain a hematocrit within range?
• How will we track symptoms (e.g., itching, headaches, and concentration issues) alongside laboratory results to assess the benefits of the treatment?
• If goals aren't met, when would we discuss adding or switching cytoreduction?

Decisions are individualized to balance efficacy, side effects, symptom relief, and monitoring needs.

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Day-to-day management centers on serial assessment, not a single result. Clinicians track hematocrit levels, review symptoms, and monitor platelet and white blood cell counts, spleen size, and treatment tolerance over time. This “whole picture” approach is commonly used in PV care. [17]

What's typically followed:

• Hematocrit and counts: Maintaining a hematocrit level below 45% reduces cardiovascular and thrombotic events (CYTO-PV); platelet and white blood cell counts are monitored alongside symptoms and spleen findings. [15]
• Symptoms: Itch (often worse after warm baths/showers), headaches, dizziness, changes in concentration, night sweats, and symptoms from reduced blood flow in tiny vessels (such as tingling or burning in the hands and feet); validated tools like the Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS) help track the burden over time. [3] [13]
• Safety checks: review of side effects and bleeding/clotting history; some patients with extreme thrombocytosis (platelet counts > 1000 × 10⁹/L) may be evaluated for acquired von Willebrand disease, as very high platelet counts can induce loss of large von Willebrand factor multimers and paradoxical bleeding. [18]

The short answer is usually not. In most people, the JAK2 gene mutation that drives polycythemia vera is an acquired (somatic) change that develops during life, not something you’re born with or pass on. Family members typically do not need routine testing just because one person has PV. [14]

There are rare families in which several relatives develop a myeloproliferative neoplasm. This reflects inherited predisposition (for example, the JAK2 “46/1” haplotype) that can slightly increase the chance of acquiring a JAK2 V617F mutation—but it still doesn’t mean PV itself is inherited or inevitable. [19]

What to discuss with your care team

If multiple close relatives have MPNs, ask whether your family history significantly alters your own monitoring plan or counseling.

Not by itself. A JAK2 mutation can be found in several myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and even in some older adults without a diagnosed blood cancer (a state called clonal hematopoiesis). About half of ET cases carry JAK2 V617F, underscoring that the mutation alone doesn’t specify which condition, if any, is present. [9] [11]

PV itself is classified as an MPN (a type of blood cancer), but clinicians don’t rely on the JAK2 result alone to make that call. They use formal criteria discussed above that combine blood count thresholds, bone marrow features, and erythropoietin levels with JAK2 status. In practice, diagnosis generally requires three major criteria or two major plus one minor, so a JAK2-positive result is only one piece of the puzzle. [9]

Clonal hematopoiesis of indeterminate potential (CHIP) means a fraction of blood-forming cells carry mutations (including JAK2) without meeting criteria for an MPN. CHIP becomes more common with age and is linked to a higher long-term risk of hematologic cancers and cardiovascular disease. Still, the absolute risk of progression to hematologic cancer remains low, which is approximately 0.5% per year in patients with mutations. [20]

1. How common is JAK2-negative PV?

Most people with PV have a JAK2 mutation, commonly the V617F variant; exon 12 variants account for many cases that are V617F-negative. Truly JAK2-negative PV is uncommon; diagnosis relies on the complete set of criteria (counts, marrow, EPO) when mutation testing is negative or indeterminate. [21]

2. What is JAK2 V617F allele burden, and should I track it?

JAK2 V617F VAF estimates the proportion of cells carrying the JAK2 V617F mutation. It’s being studied for risk correlations, but it isn’t required for diagnosis, and most follow-up focuses on hematocrit <45%, other counts, and symptoms. Ask your team whether JAK2 V617F VAF would change decisions in your case. [3]

3. Are JAK2 inhibitors used in polycythemia vera?

Yes. Certain JAK2 inhibitors are indicated for the treatment of adult patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. Clinical studies have shown benefits in hematocrit control and symptom relief; however, treatment may be associated with adverse events such as anemia, thrombocytopenia, or infections. Treatment decisions, including whether a JAK2 inhibitor is appropriate, should be individualized and discussed with your doctor or healthcare professional. [22] [23] [24]

4. Beyond hematocrit, what other parameters are monitored?

Ongoing care typically involves monitoring platelet counts, white blood cell counts, spleen findings, treatment tolerance, and symptoms (e.g., itching, headaches, concentration difficulties). Many clinics use the validated MPN-SAF TSS (MPN-10) to track symptom burden over time. [25]

5. Can symptoms guide care even when labs look "okay"?

Yes, symptom trends (itch, headaches, night sweats, early satiety, fatigue) provide essential context for adjusting plans alongside lab targets. Structured tools, such as MPN-SAF TSS, enable patients and clinicians to observe changes over time. [25]

6. Why is the hematocrit goal emphasized so strongly?

Randomized study data (CYTO-PV) show that maintaining a hematocrit below 45% reduces cardiovascular events and major thrombosis compared with maintaining a hematocrit between 45% and 50%, so most guidance centers focus on this target. [15]

• CBC – Complete blood count
• CHIP – Clonal hematopoiesis of indeterminate potential
• EPO – Erythropoietin
• ET – Essential thrombocythemia
• Hct – Hematocrit
• Hgb – Hemoglobin
• ICC – International Consensus Classification
• JAK – Janus kinase
• JAK2 – Janus kinase 2
• MPN – Myeloproliferative neoplasm
• MPN-SAF TSS – Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score
• MPN-10 – 10-item version of the MPN-SAF TSS
• PMF – Primary myelofibrosis
• PV – Polycythemia vera
• VAF – Variant allele fraction
• V617F – Valine-to-phenylalanine substitution at amino acid 617

1. Mengie Ayele, T., Tilahun Muche, Z., Behaile Teklemariam, A., Bogale Kassie, A., & Chekol Abebe, E. (2022). Role of JAK2/STAT3 Signaling Pathway in the Tumorigenesis, Chemotherapy Resistance, and Treatment of Solid Tumors: A Systemic Review. Journal of inflammation research, 15, 1349–1364. https://doi.org/10.2147/JIR.S353489
2. Morris, R., Kershaw, N. J., & Babon, J. J. (2018). The molecular details of cytokine signaling via the JAK/STAT pathway. Protein science : a publication of the Protein Society, 27(12), 1984–2009. https://doi.org/10.1002/pro.3519
3. Tefferi A, Barbui T. Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023 Sep;98(9):1465-1487. doi: 10.1002/ajh.27002. Epub 2023 Jun 26. PMID: 37357958.
4. Lu X, Chang R. Polycythemia Vera. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
5. Griesshammer, M., Gisslinger, H. & Mesa, R. Current and future treatment options for polycythemia vera. Ann Hematol 94, 901–910 (2015). https://doi.org/10.1007/s00277-015-2357-4
6. Pardanani, A., Lasho, T. L., Finke, C., Hanson, C. A., & Tefferi, A. (2007). Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia, 21(9), 1960–1963. https://doi.org/10.1038/sj.leu.2404810
7. Scott, L. M., Tong, W., Levine, R. L., Scott, M. A., Beer, P. A., Stratton, M. R., ... & Green, A. R. (2007). JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. New England Journal of Medicine, 356(5), 459-468.
8. Scott, L. M. (2011). The JAK2 exon 12 mutations: a comprehensive review. American journal of hematology, 86(8), 668-676.
9. Arber, D. A., Orazi, A., Hasserjian, R. P., Borowitz, M. J., Calvo, K. R., Kvasnicka, H. M., ... & Tefferi, A. (2022). International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood, The Journal of the American Society of Hematology, 140(11), 1200-1228.
10. Raedler L. A. (2014). Diagnosis and Management of Polycythemia Vera: Proceedings from a Multidisciplinary Roundtable. American health & drug benefits, 7(7 Suppl 3), S36–S47.
11. Shlush, L. I. (2018). Age-related clonal hematopoiesis. Blood, The Journal of the American Society of Hematology, 131(5), 496-504.
12. Lee, A. J., Kim, S. G., Nam, J. Y., Yun, J., Ryoo, H. M., & Bae, S. H. (2021). Clinical features and outcomes of JAK2 V617F-positive polycythemia vera and essential thrombocythemia according to the JAK2 V617F allele burden. Blood research, 56(4), 259–265. https://doi.org/10.5045/br.2021.2021089
13. Benevolo, G., Vassallo, F., Urbino, I., & Giai, V. (2021). Polycythemia Vera (PV): Update on Emerging Treatment Options. Therapeutics and clinical risk management, 17, 209–221. https://doi.org/10.2147/TCRM.S213020
14. Jones, A. V., & Cross, N. C. (2013). Inherited predisposition to myeloproliferative neoplasms. Therapeutic advances in hematology, 4(4), 237–253. https://doi.org/10.1177/2040620713489144
15. Duminuco, A., Harrington, P., Harrison, C., & Curto-Garcia, N. (2023). Polycythemia vera: barriers to and strategies for optimal management. Blood and Lymphatic Cancer: Targets and Therapy, 77-90.
16. Marchioli, R., Finazzi, G., Specchia, G., Cacciola, R., Cavazzina, R., Cilloni, D., ... & Barbui, T. (2013). Cardiovascular events and intensity of treatment in polycythemia vera. New England Journal of Medicine, 368(1), 22-33.
17. Verstovsek, S., Pemmaraju, N., Reaven, N. L., Funk, S. E., Woody, T., Valone, F., & Gupta, S. (2023). Real-world treatments and thrombotic events in polycythemia vera patients in the USA. Annals of hematology, 102(3), 571–581. https://doi.org/10.1007/s00277-023-05089-6
18. Awada, H., Voso, M. T., Guglielmelli, P., & Gurnari, C. (2020). Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding. Cancers, 12(7), 1746. https://doi.org/10.3390/cancers12071746
19. Anelli, L., Zagaria, A., Specchia, G., & Albano, F. (2018). The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?. International journal of molecular sciences, 19(4), 1152. https://doi.org/10.3390/ijms19041152
20. Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., ... & Ebert, B. L. (2014). Age-related clonal hematopoiesis associated with adverse outcomes. New England Journal of Medicine, 371(26), 2488-2498.
21. Geetha, J. P., Arathi, C. A., Shalini, M., & Srinivasa Murthy, A. G. (2010). JAK2 Negative Polycythemia Vera. Journal of laboratory physicians, 2(2), 114–116. https://doi.org/10.4103/0974-2727.72215
22. Jakafi (ruxolitinib) tablets, Prescribing Information. Incyte Corporation.
23. Jakavi, INN-ruxolitinib – Summary of product characteristics (SmPC). European Medicines Agency.
24. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426–435. https://doi.org/10.1056/NEJMoa1409002
25. Emanuel, R. M., Dueck, A. C., Geyer, H. L., Kiladjian, J. J., Slot, S., Zweegman, S., ... & Mesa, R. A. (2012). Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. Journal of clinical oncology, 30(33), 4098-4103.