Do polycythemia vera and acute myeloid leukemia share any genetic mutations?

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Last updated: February 19, 2026 • View editorial policy

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Genetic Overlap Between Polycythemia Vera and Acute Myeloid Leukemia

Yes, polycythemia vera (PV) and acute myeloid leukemia (AML) share significant genetic overlap, most notably through JAK2 mutations and additional non-driver mutations that accumulate during disease progression, with PV representing a clonal stem cell disorder that carries inherent risk of leukemic transformation.

Shared JAK2 Mutations

  • JAK2 V617F mutation is present in >95% of PV patients and represents the primary driver mutation in this myeloproliferative neoplasm 1, 2.
  • JAK2 exon 12 mutations account for 2-4% of PV cases in patients who are JAK2 V617F-negative, providing an alternative mechanism of JAK-STAT pathway activation 2.
  • When PV transforms to AML, the JAK2 mutation persists in the leukemic clone, demonstrating direct genetic continuity between the two diseases 3.
  • Amplification of the JAK2 gene on chromosome 9p has been documented in cases of PV transforming to AML, with one case report showing amplification of the 9p22-p24.3 region including JAK2, MLLT3, JMJD2C, and SMARCA2 genes 3.

Accumulation of Non-Driver Mutations

The genetic bridge between PV and AML involves progressive acquisition of additional mutations beyond JAK2:

  • Patients with PV who later progress to AML show 83% frequency of non-driver mutations at first sample, compared to only 18% in patients who remain stable for >10 years 4.
  • The mutation acquisition rate is dramatically higher in patients destined for AML transformation: 25.6 new mutations per 100 person-years versus 1.7 per 100 person-years in stable patients 4.
  • Specific mutations shared between PV and AML include:
    • ASXL1 (15% frequency in PV, strongly associated with AML transformation, p<0.0001) 4, 5
    • TET2 (18% frequency in PV) 5
    • TP53 (associated with AML risk, p=0.01) 4
    • SRSF2 (prognostically adverse, associated with AML, p<0.0001) 4, 5
    • IDH1/2 (associated with both AML and myelofibrosis transformation, p<0.0001) 4, 5
    • RUNX1 (prognostically adverse, associated with AML, p<0.0001) 4, 5
    • U2AF1 (prognostically adverse) 5

Cytogenetic Abnormalities

  • Abnormal karyotype is present in 15-20% of PV patients at diagnosis, with the most frequent sole abnormalities being trisomy 9 (5%), loss of chromosome Y (4%), trisomy 8 (3%), and 20q deletion (3%) 5.
  • Gains on chromosome 9p are among the most common cytogenetic abnormalities in both PV and during transformation, suggesting amplification of genes in this region plays a crucial role in disease evolution 3.
  • Complex karyotypes develop with disease progression, and abnormal karyotype is an independent adverse prognostic factor for survival in PV 5.

Clinical Implications for Transformation Risk

The 20-year risk of AML transformation in PV is approximately 4%, but this risk is substantially modified by genetic factors 5:

  • Presence of additional mutations at diagnosis is the unique risk factor for acquiring new genetic events (HR 2.7,95% CI 1.1-6.8, p=0.03) 4.
  • Patients with additional mutations at first sample have significantly higher risk of AML (HR 12.2,95% CI 2.6-57.1, p=0.001) 4.
  • The combined incidence of prognostically adverse mutations (SRSF2, IDH2, RUNX1, U2AF1) is 5-10% in PV patients 5.

Mechanistic Convergence

  • PV is fundamentally a clonal stem cell disorder affecting both myeloid and lymphoid lineages, establishing the biological framework for transformation 1.
  • Germline risk variants at JAK2 predispose to somatic point mutations within JAK2, whose allelic dosage can be further increased by uniparental disomy (UPD) on chromosome 9p, creating a convergent mechanism for disease progression 6.
  • Somatic 9p UPD magnitude is strongly associated with JAK2 V617F dosage (r²=0.74, p=4.8E-12), suggesting UPD preferentially expands the mutant clone 6.

Practical Clinical Monitoring

Next-generation sequencing (NGS) may identify PV patients with high genetic instability:

  • NGS testing for non-driver mutations is useful to identify the minority of PV and ET patients with increased risk of AML transformation 4.
  • Patients developing cytopenia under hydroxyurea therapy show higher probability of harboring additional mutations and subsequent AML risk 4.
  • Over 50% of PV patients harbor DNA sequence variants/mutations other than JAK2, emphasizing the genetic complexity underlying this disease 5.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Management of JAK2 Exon 12‑Mutated Polycythemia Vera

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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