Eritrositozun Genetik İzleri: Tam Kan Sayımı Parametreleri ve/veya Serum Eritropoetin Düzeyi ile JAK2 Mutasyonunun Varlığını Belirleyebilir miyiz?

Year 2026, Volume: 79 Issue: 1, 98 - 107, 27.03.2026

Derya Koyun , Fatma Söylemez , Ömer Yakar

https://doi.org/10.65092/autfm.1827667

https://izlik.org/JA76JY78AZ

Abstract

Giriş: Bu çalışmada, yüksek rakımda yaşayan eritrositozlu hastalarda hemogram, biyokimyasal parametreler ve serum eritropoietin (EPO) düzeyleri kullanılarak JAK2V617F mutasyonunun varlığını öngörmeyi amaçladık.
Yöntem: Bu retrospektif çalışmada, 2022–2025 yılları arasında eritrositoz nedeniyle başvuran ve en az bir yıldır yaklaşık 1800 metre rakımda yaşayan 186 hasta değerlendirildi. Eritrositoz varlığı, 2022 Dünya Sağlık Örgütü kriterlerine göre konuldu. Hastaların demografik özellikleri, hematolojik ve biyokimyasal parametreleri ile serum EPO düzeyleri, JAK2V617F mutasyonunun varlığına göre karşılaştırıldı. Ardından çok değişkenli lojistik regresyon ve ROC analizleri uygulandı.
Bulgular: Çalışmaya dahil edilen 186 hastanın 151’i (%81.2) JAK2V617F negatif, 35’i (%18.8) pozitifti. Mutasyon pozitif hastalar anlamlı derecede daha yaşlıydı (p < 0.001). Tek değişkenli analizlerde; hemoglobin (p = 0.015), Ortalama Eritrosit Hacmi (MCV) (p = 0.029), Ortalama Eritrosit Hemoglobini (MCH) (p < 0.001), Ortalama Eritrosit Hemoglobin Konsantrasyonu (MCHC) (p < 0.001) ve EPO (p < 0.001) düzeylerinin düşük olduğu; buna karşılık Eritrosit Sayısı (RBC) (p = 0.001), Trombosit Sayısı (PLT) (p < 0.001), Eritrosit Dağılım Genişliği (RDW) (p < 0.001) ve Laktat Dehidrogenaz (LDH) (p < 0.001) düzeylerinin yüksek olduğu saptandı. Çok değişkenli lojistik regresyon analizinde RBC (p = 0.023) ve PLT (p = 0.006) mutasyon pozitifliği için bağımsız belirteçler olarak saptandı. EPO (p = 0.057) ve Ortalama Trombosit Hacmi (MPV) (p = 0.092) sınırda anlamlılık gösterirken, JAKPOT skoru modelde anlamlı bulunmadı (p = 0.176). ROC analizine göre PLT, JAK2V617F mutasyonunu ayırt etmede en güçlü parametreydi (AUC: 0.849); MPV düşük tanısal performans gösterdi. RBC ≥ 6.61 × 10¹²/L ve PLT ≥ 336.5 × 10⁹/L eşik değerleri, mutasyon öngörüsünde yüksek doğruluk sağladı.
Sonuç: RBC ve PLT düzeyleri, JAK2V617F mutasyonunun varlığını öngörmede güçlü ve maliyet-etkin belirteçlerdir. EPO düzeylerinin katkısı sınırlı kalmış, JAKPOT skoru ise etkisiz bulunmuştur. Eritrositozun değerlendirilmesinde, özellikle yüksek rakım gibi çevresel faktörlerin tanısal parametrelerin yorumunu önemli ölçüde etkileyebileceği dikkate alınmalıdır.

Keywords

Eritrositoz , Trombosit Sayısı , JAK2V617F mutasyonu , eritrosit sayısı

Ethical Statement

Araştırma, 02.07.2025 tarihli ve 2025/06-26-E.7530 sayılı karar ile etik kurul tarafından uygun bulunmuştur

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Genetic Markers of Erythrocytosis: Can the Presence of JAK2 Mutation Be Determined via Complete Blood Count Parameters and/or Serum Erythropoietin Level?

https://izlik.org/JA76JY78AZ

Abstract

Introduction: In our study, we aimed to predict the presence of the JAK2V617F mutation using haemogram, biochemical parameters, and serum erythropoietin (EPO) levels in patients with erythrocytosis living at high altitudes.
Methods: In this retrospective study, 186 patients who presented with erythrocytosis between 2022 and 2025 and had resided at an altitude of ~1800 metres for at least one year were examined. The presence of erythrocytosis was determined according to the 2022 World Health Organisation criteria. Demographic, haematological, and biochemical parameters, as well as serum EPO levels, of the patients were compared according to the presence of the JAK2V617F mutation. Multivariate logistic regression and ROC analysis were then applied.
Results: The study included 186 patients; 151 (81.2%) were negative for the JAK2V617F mutation, and 35 (18.8%) were positive. Mutation-positive patients were significantly older ( p < 0.001). Univariate analyses revealed decreased levels of haemoglobin (p = 0.015), Mean Corpuscular Volume (MCV) (p = 0.029),
Mean Corpuscular Hemoglobin (MCH) (p < 0.001), Mean Corpuscular Hemoglobin Concentration (MCHC) (p < 0.001), and EPO (p < 0.001). They significantly increased proliferative parameters, including Red Blood Cell Count (RBC) (p = 0.001), Platelet Count (PLT) (p < 0.001), Red Cell Distribution Width (RDW) (p <0.001), and Lactate Dehydrogenase (LDH) (p < 0.001). When these variables were analysed by multivariate logistic regression analysis, RBC (p = 0.023) and PLT (p = 0.006) were found to be independent predictors of mutation positivity. EPO (p = 0.057) and Mean Platelet Volume (MPV) (p = 0.092) showed borderline significance, whereas the JAKPOT score was not significant in the multivariate model (p = 0.176). According to ROC analysis, PLT was the most powerful parameter in differentiating JAK2V617F mutation (AUC: 0.849), whereas MPV had low diagnostic performance. RBC ≥6.61 × 10¹²/L and PLT ≥336.5 × 10⁹/L thresholds provided high accuracy in mutation prediction.
Conclusion: RBC and PLT levels are robust and cost-effective markers for predicting the presence of JAK2V617F mutation. EPO levels made a limited contribution. Otherwise, the JAKPOT score was ineffective. Environmental factors, especially high altitude, should be considered when interpreting diagnostic markers in erythrocytosis.

Keywords

Erythrocytosis , Platelet Count , JAK2V617F mutation , red blood cell count

Ethical Statement

The study received ethical approval from the local ethics committee (date: 2.7.2025, no: 2025/06-26- E.7530).

Supporting Institution

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Project Number

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Thanks

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References

• Thiele J, Kvasnicka HM, Orazi A, et al. The international consensus classification of myeloid neoplasms and acute leukemias: myeloproliferative neoplasms. Am J Hematol. 2023;98 (1):166–179.
• Tefferi A, Vannucchi AM, Barbui T. Polycythemia vera: historical oversights, diagnostic details, and therapeutic views. Leukemia. 2021;35(12):3339–3351.
• Chin-Yee B, Bhai P, Cheong 1 et al. A rational approach to JAK2 mutation testing in patients with elevated hemoglobin: results from the JAK2 pre-diction cohort (JAKPOT) study. J Gen 1ntern Med. 2023;38 (8):1828-1833. Kucine N. Myeloproliferative neoplasms in children, adolescents, and young adults. Curr Hematol Malig Rep. 2020;15(2):141–148.
• Liu D, Xu Z, Zhang P, et al. Iron deficiency in JAK2 exon 12 and JAK2-V617F mutated polycythemia vera. Blood Cancer J. 2021;11(9):154.
• Alkhaldy HY, Alqarni AM, Bhakeet OSE, et al. Diagnostic performance of red blood cell indices, serum erythropoietin, and JAK2 mutation testing for the evaluation of polycythemia vera at high altitude. Blood. 2023;142:6398.
• Jia C, Sun T, Yang R, et al. Deciphering neutrophil heterogeneity and thrombosis- related alterations in JAK2V617F-mutated myeloproliferative neoplasms through multi-omics and single-cell transcriptome analysis. Blood. 2024;144:3138.
• Senecal J, Madan Y, Rajkumar S, et al. Diagnostic accuracy of erythropoietin and JAKPOT in predicting JAK2-positive erythrocytosis: a retrospective cohort study. Blood. 2024;144:5017.
• Miura S, Ueda K, Misaka T, et al. Characteristics and consequences of platelets derived from JAK2-mutated megakaryocytes. Blood. 2024;144:3140.
• Koh JS, Seo W, Kang S, et al. Clinical features and outcomes of JAK2 unmutated erythrocytosis. Blood Res. 2025;60(1):20.
• Koca U, Sahinera ES, Kosemehmetoglu OS, et al. Hemoglobin levels for the diagnosis of polycythemia vera: how high is high enough? Eur J Intern Med. 2025; 137: 144-145 https://doi.org/10.1016/j.ejim.2025.02.018
• Cheong I, Bhai P, Chin-Yee B, et al. A prediction rule to guide JAK2 mutation testing in patients with elevated hemoglobin levels. London Health Sciences Centre. 2021.
• Chin-Yee B, Cheong I, Matyashin M, et al. Serum erythropoietin levels in 696 patients investigated for erythrocytosis with JAK2 mutation analysis. Am J Hematol. 2022; E150.
• Eren R, Karismaz A, Arslan C, et al. Serum erythropoietin level in polycythemia vera: is a new cut-off possible? Indian J Hematol Blood Transfus. 2025; 41.4: 951-955.
• Lupak O, Han X, Xie P, et al. The role of a low erythropoietin level for the polycythemia vera diagnosis. Blood Cells Mol Dis. 2020;80:102355.