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MPH Hastalarında JAK2 F617 Allel Yükü ile Hematolojik Parametrelerin İlişkisi

Yıl 2025, Cilt: 27 Sayı: 1, 100 - 103, 26.04.2025
https://doi.org/10.24938/kutfd.1634622

Öz

Amaç: JAK2 genindeki bir nokta mutasyonu, fenilalanin yerine valinin geçmesi (JAK2 V617F) ile sonuçlanmakla beraber, polisitemi vera, esansiyel trombositemi, idiyopatik miyelofibroz, miyelodisplastik sendromlar, kronik miyelomonositik lösemi, sistemik mastositoz, kronik nötrofilik lösemi ve eozinofilik bozukluklar gibi miyeloproliferatif bozukluklarla ilişkilendirilmiştir.
Gereç ve Yöntemler: Miyeloproliferatif bozukluk tanılı hastalarda JAK2 V617F mutasyonu alel yükü qPCR yöntemi ile incelenmiştir. F617 aleli, %50'den az ve fazla mutasyon yükü gruplarını içeren standart bir kalibrasyon eğrisi kullanılarak hesaplanmıştır.
Bulgular: Yabanıl tip (wt), %50'den fazla ve düşük gruplar arasında eritrosit, hematokrit, trombosit ve lökosit düzeyleri açısından anlamlı bir ilişki bulundu. Wt ve %50'den fazla gruplar arasında hemoglobin düzeyleri açısından istatistiksel olarak anlamlı bir ilişki bulunmuştur. Mutasyonel yük artışının trombosit düzeyleri hariç eritrosit, hematokrit ve lökosit düzeylerini indüklediği gösterilmiştir.
Sonuç: Miyeloproliferatif bozukluğu olan hastalarda JAK2 gen mutasyonunun rutin taraması endike olarak görünmektedir.

Kaynakça

  • Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-1061.
  • Verstovsek S, Silver RT, Cross NC, et al. JAK2 V617F mutational frequency in polycythemia vera: 100%, >90%, less? Leukemia. 2006;20:2067.
  • Passamonti F, Rumi E, Pietra D, et al. A prospective study of 338 patients with polycythemia vera: The impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24:1574-1579.
  • Zhang S, Qiu H, Fischer BS, et al. JAK2 V617F patients with essential thrombocythemia present with clinical features of polycythemia vera. Leuk Lymphoma. 2008;49:696-699.
  • Rane SG, Reddy EP. JAKs, STATs and SRC kinases in hematopoiesis. Oncogene. 2002;21(21):3334-3358.
  • Akada H, Yan D, Zou H, et al. Conditional expression of heterozygous or homozygous JAK2 V617F from its endogenous promoter induces a polycythemia vera-like disease. Blood. 2010;115(17):3589-3597.
  • Guglielmelli P, Vannucchi AM. Recent advances in diagnosis and treatment of chronic myeloproliferative neoplasms. F1000 Med Rep. 2010;2:16.
  • Silver RT, Vandris K, Wang YL, et al. JAK2 (V617F) allele burden in polycythemia vera correlates with grade of myelofibrosis, but is not substantially affected by therapy.Leuk Res. 2011;35:177-182.
  • El-Moneim AA, Kratz CP, Böll S, et al. Essential versus reactive thrombocythemia in children: Retrospective analyses of 12 cases. Pediatr Blood Cancer. 2007;49:52- 55.
  • Primignani M, Barosi G, Bergamaschi G, et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006;44:1528-1534.
  • Traulsen A, Pacheco JM, Luzzatto L, et al. Somatic mutations and the hierarchy of hematopoiesis. Bioessays. 2010;32:1003-1008.
  • Kralovics R, Passamonti F, Buser AS, et al. A gain-of- function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779-1790.
  • Bahsi T, Yigenoglu TN. CALR, JAK2 and MPL Genes mutations in myeloproliferative neoplasms, single center experience. Acta Oncologica Turcica. 2019;52:388-392.
  • Nangalia J, Green TR. The evolving genomic landscape of myeloproliferative neoplasms. Hematol Am Soc Hematol Educ Program. 2014;2014(1):287-296.
  • Chen CC, Chen JL, Lin AJ, et al. Association of JAK2 V617F allele burden and clinical correlates in polycythemia vera: A systematic review and meta- analysis. Ann Hematol. 2024;103(6):1947-1965.
  • Alvarez-Larrán A, Bellosillo B, Pereira A, et al. JAK2 V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events. Am J Hematol. 2014;89(5):517-523.
  • Vannucchi AM, Antonioli E, Guglielmelli P, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2 (V617F) allele burden. Leukemia. 2007;21(9):1952-1959.
  • Stein BL, Saraf S, Sobol U, et al. Age-related differences in disease characteristics and clinical outcomes in polycythemia vera. Leuk Lymphoma. 2013;54(9):1989- 1995.
  • Lee AJ, Kim SG, Nam JY, et al. Clinical features and outcomes of JAK2 V617F-positive polycythemia vera and essential thrombocythemia according to the JAK2 V617F allele burden. Blood Res. 2021;56(4):259-265.
  • Okabe M, Yamaguchi H, Usuki K, et al. Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2 V617F, JAK2 Ex12del, and MPL W515L/K mutations. Leuk Res. 2016;40:68-76.

ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS

Yıl 2025, Cilt: 27 Sayı: 1, 100 - 103, 26.04.2025
https://doi.org/10.24938/kutfd.1634622

Öz

Objective: A point mutation in the JAK2 gene, resulting in the substitution of valine for phenylalanine (JAK2 V617F), has been associated with myeloproliferative disorders such as polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis, myelodysplastic syndromes, chronic myelomonocytic leukemia, systemic mastocytosis, chronic neutrophilic leukemia, and eosinophilic disorders.
Material and Methods: The relation of JAK2 V617F mutation has been studied in myeloproliferative disorder patients by qPCR. The F617 allele was calculated using a standard calibration curve, including less and more than 50% mutational load groups.
Results: A significant relation was found among wild type (wt), less and more than 50% groups, Regarding erythrocyte, hematocrit, platelet, and leukocyte levels. A statistically significant relation was found between wt and more than 50% of groups regarding hemoglobin levels. The mutational load increase has been shown to induce erythrocyte, hematocrit, and leukocyte levels, except platelet levels.
Conclusion: In patients with myeloproliferative disorders, qPCR screening of JAK2 gene mutation is indicated.

Kaynakça

  • Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-1061.
  • Verstovsek S, Silver RT, Cross NC, et al. JAK2 V617F mutational frequency in polycythemia vera: 100%, >90%, less? Leukemia. 2006;20:2067.
  • Passamonti F, Rumi E, Pietra D, et al. A prospective study of 338 patients with polycythemia vera: The impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia. 2010;24:1574-1579.
  • Zhang S, Qiu H, Fischer BS, et al. JAK2 V617F patients with essential thrombocythemia present with clinical features of polycythemia vera. Leuk Lymphoma. 2008;49:696-699.
  • Rane SG, Reddy EP. JAKs, STATs and SRC kinases in hematopoiesis. Oncogene. 2002;21(21):3334-3358.
  • Akada H, Yan D, Zou H, et al. Conditional expression of heterozygous or homozygous JAK2 V617F from its endogenous promoter induces a polycythemia vera-like disease. Blood. 2010;115(17):3589-3597.
  • Guglielmelli P, Vannucchi AM. Recent advances in diagnosis and treatment of chronic myeloproliferative neoplasms. F1000 Med Rep. 2010;2:16.
  • Silver RT, Vandris K, Wang YL, et al. JAK2 (V617F) allele burden in polycythemia vera correlates with grade of myelofibrosis, but is not substantially affected by therapy.Leuk Res. 2011;35:177-182.
  • El-Moneim AA, Kratz CP, Böll S, et al. Essential versus reactive thrombocythemia in children: Retrospective analyses of 12 cases. Pediatr Blood Cancer. 2007;49:52- 55.
  • Primignani M, Barosi G, Bergamaschi G, et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006;44:1528-1534.
  • Traulsen A, Pacheco JM, Luzzatto L, et al. Somatic mutations and the hierarchy of hematopoiesis. Bioessays. 2010;32:1003-1008.
  • Kralovics R, Passamonti F, Buser AS, et al. A gain-of- function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779-1790.
  • Bahsi T, Yigenoglu TN. CALR, JAK2 and MPL Genes mutations in myeloproliferative neoplasms, single center experience. Acta Oncologica Turcica. 2019;52:388-392.
  • Nangalia J, Green TR. The evolving genomic landscape of myeloproliferative neoplasms. Hematol Am Soc Hematol Educ Program. 2014;2014(1):287-296.
  • Chen CC, Chen JL, Lin AJ, et al. Association of JAK2 V617F allele burden and clinical correlates in polycythemia vera: A systematic review and meta- analysis. Ann Hematol. 2024;103(6):1947-1965.
  • Alvarez-Larrán A, Bellosillo B, Pereira A, et al. JAK2 V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events. Am J Hematol. 2014;89(5):517-523.
  • Vannucchi AM, Antonioli E, Guglielmelli P, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2 (V617F) allele burden. Leukemia. 2007;21(9):1952-1959.
  • Stein BL, Saraf S, Sobol U, et al. Age-related differences in disease characteristics and clinical outcomes in polycythemia vera. Leuk Lymphoma. 2013;54(9):1989- 1995.
  • Lee AJ, Kim SG, Nam JY, et al. Clinical features and outcomes of JAK2 V617F-positive polycythemia vera and essential thrombocythemia according to the JAK2 V617F allele burden. Blood Res. 2021;56(4):259-265.
  • Okabe M, Yamaguchi H, Usuki K, et al. Clinical features of Japanese polycythemia vera and essential thrombocythemia patients harboring CALR, JAK2 V617F, JAK2 Ex12del, and MPL W515L/K mutations. Leuk Res. 2016;40:68-76.
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Özgün Araştırma
Yazarlar

Sezen Guntekin Ergun 0000-0002-7133-5049

Abdullatif Bakır 0000-0002-3931-4168

Ferda Perçin 0000-0001-9317-8155

Mehmet Ali Ergun 0000-0001-9696-0433

Yayımlanma Tarihi 26 Nisan 2025
Gönderilme Tarihi 6 Şubat 2025
Kabul Tarihi 25 Şubat 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 27 Sayı: 1

Kaynak Göster

APA Guntekin Ergun, S., Bakır, A., Perçin, F., Ergun, M. A. (2025). ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS. The Journal of Kırıkkale University Faculty of Medicine, 27(1), 100-103. https://doi.org/10.24938/kutfd.1634622
AMA Guntekin Ergun S, Bakır A, Perçin F, Ergun MA. ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS. Kırıkkale Üni Tıp Derg. Nisan 2025;27(1):100-103. doi:10.24938/kutfd.1634622
Chicago Guntekin Ergun, Sezen, Abdullatif Bakır, Ferda Perçin, ve Mehmet Ali Ergun. “ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS”. The Journal of Kırıkkale University Faculty of Medicine 27, sy. 1 (Nisan 2025): 100-103. https://doi.org/10.24938/kutfd.1634622.
EndNote Guntekin Ergun S, Bakır A, Perçin F, Ergun MA (01 Nisan 2025) ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS. The Journal of Kırıkkale University Faculty of Medicine 27 1 100–103.
IEEE S. Guntekin Ergun, A. Bakır, F. Perçin, ve M. A. Ergun, “ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS”, Kırıkkale Üni Tıp Derg, c. 27, sy. 1, ss. 100–103, 2025, doi: 10.24938/kutfd.1634622.
ISNAD Guntekin Ergun, Sezen vd. “ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS”. The Journal of Kırıkkale University Faculty of Medicine 27/1 (Nisan2025), 100-103. https://doi.org/10.24938/kutfd.1634622.
JAMA Guntekin Ergun S, Bakır A, Perçin F, Ergun MA. ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS. Kırıkkale Üni Tıp Derg. 2025;27:100–103.
MLA Guntekin Ergun, Sezen vd. “ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS”. The Journal of Kırıkkale University Faculty of Medicine, c. 27, sy. 1, 2025, ss. 100-3, doi:10.24938/kutfd.1634622.
Vancouver Guntekin Ergun S, Bakır A, Perçin F, Ergun MA. ASSOCIATION OF JAK2 F617 ALLELE BURDEN WITH HEMATOLOGICAL PARAMETERS IN MPD PATIENTS. Kırıkkale Üni Tıp Derg. 2025;27(1):100-3.

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