POLİSİTEMİA VERA OLGULARINDA JAK2 V617F MUTASYON SIKLIĞI VE LABORATUVAR BULGULARI İLE İLİŞKİSİ

Year 2021, , 573 - 577, 30.12.2021

Kuyaş Hekimler Öztürk , Muhammet Yusuf Tepebaşı , Halil Özbaş , Pınar Koşar

https://doi.org/10.17343/sdutfd.978526

Abstract

Amaç
Polisitemia vera (PV) miyeloid hücrelerin klonal proliferasyonu
ile karakterize klonal bir hastalıktır. Janus
tirozin kinaz 2 (JAK2) geni V617F mutasyonunun hastalığın
moleküler patogenezinin temelini oluşturduğu
gösterilmiştir. Bu çalışmada PV’lı hastalarda JAK2
V617F mutasyon sıklığı ve hematolojik parametreler
ile arasındaki ilişkinin incelenmesi amaçlanmıştır.
Gereç ve Yöntem
Bu retrospektif kohort çalışmasına BCR-ABL negatif
PV tanılı 18’i kadın, 60'ı erkek olmak üzere toplam 78
hasta dahil edildi. Hastalara ait poliklinik dosyaları incelenerek
demografik özellikler, laboratuvar bulguları
ve JAK2 V617F mutasyon analiz sonuçları kaydedildi.
JAK2 V617F mutasyon analizleri Real-Time PCR
yöntemi ile yapıldı.
Bulgular
Çalışmaya dahil edilen 78 PV hastasının 21’inde
(%26,9) JAK2 V617F mutasyonu saptandı. Mutasyon
varlığı ve cinsiyet arasında fark saptanmadı (p>0.05).
Mutasyon pozitifliğine göre yapılan gruplandırmada
JAK2 V617F mutasyonu taşıyan hastalarda yaş, RBC,
RDW ve PLT seviyeleri açısından anlamlı derecede
yüksek saptanırken (sırasıyla, p=0,000; p=0,030;
p=0,028; p=0,029), serum demir düzeyi açısından
anlamlı derecede düşük saptandı (p=0,036) . WBC,
HB ve HCT seviyeleri her iki grupta benzerdi (p>0,05).
Sonuç
Mutasyonun prognostik değerini ve klinik ve laboratuvar
değişkenleriyle ilişkisini göstermek için daha kapsamlı
prospektif çalışmalara ihtiyaç vardır.

Keywords

Miyeloproliferatif bozukluklar, polisitemia vera, JAK2 V617F

JAK2 V617F MUTATION FREQUENCY IN POLYCYTHEMIA VERA CASES AND ITS RELATIONSHIP WITH LABORATORY FINDINGS

Abstract

Objective
Polycythemia vera (PV) is a clonal disease
characterized by clonal proliferation of myeloid cells.
It has been shown that the Janus tyrosine kinase 2
(JAK2) gene V617F mutation forms the basis of the
molecular pathogenesis of the disease. In this study,
it was aimed to examine the relationship between
JAK2 V617F mutation frequency and hematological
parameters in patients with PV.
Material and Methods
A total of 78 patients, 18 female and 60 male, with
PV were included in this retrospective cohort study.
Demographic characteristics, laboratory findings and
JAK2 V617F mutation analysis results were recorded
by examining the outpatient clinic files of the patients.
JAK2 V617F mutation analyzes were performed by
Real-Time PCR method.
Results
JAK2 V617F mutation was detected in 21 (26.9%)
of 78 PV patients included in the study. There was
no difference between the presence of mutation and
gender (p>0.05). In the grouping made according to
mutation positivity, while age, RBC, RDW and PLT
levels were found to be significantly higher in patients
with JAK2 V617F mutation (respectively, p=0.000;
p=0.030; p=0.028; p=0.029), serum iron level was
found to be significantly lower. (p=0.036). WBC, HB
and HCT levels were similar in both groups (p>0.05).
Conclusion
More comprehensive prospective studies are needed
to demonstrate the prognostic value of the mutation
and its relationship with clinical and laboratory
variables.

Keywords

Myeloproliferative disorders, polycythemia vera, JAK2 V617F

References

• 1. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood. 2005;106(6):2162-8.
• 2. Zhang S, Qiu H, Fischer BS, Li W, Duan L, Sun X, et al. JAK2 V617F patients with essential thrombocythemia present with clinical features of polycythemia vera. Leuk Lymphoma. 2008 Apr;49(4):696-9.
• 3. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-90.
• 4. Zhao S, Zhang X, Xu Y, Feng Y, Sheng W, Cen J, et al. Impact of JAK2 V617F Mutation Burden on Disease Phenotype in Chinese Patients with JAK2 V617F-positive Polycythemia Vera (PV) and Essential thrombocythemia (ET). Int J Med Sci 2016 ;13(1):85.
• 5. Geetha JP, Arathi CA, Shalini M, Srinivasa Murthy AG. JAK2 Negative Polycythemia Vera. J Lab Physicians. 2010;2(2):114-6.
• 6. Yönal İ, Sargın F. Polisitemia Vera: Patogenez, Teşhis Ve Tedavide Güncel Bilgiler. İstanbul Tıp Fakültesi Derg 2015;78(3):83–91.
• 7. Landolfi R, Nicolazzi MA, Porfidia A, Di Gennaro L. Polycythemia vera. Intern Emerg Med 2010;5(5):375–84.
• 8. Kaushansky K. The chronic myeloproliferative disorders and mutation of JAK2: Dameshek's 54 year old speculation comes of age. Best Pract Res Clin Haematol. 2007;20(1):5-12.
• 9. Nussenzveig RH, Swierczek SI, Jelinek J, Gaikwad A, Liu E, Verstovsek S, et al. Polycythemia vera is not initiated by JAK2V617F mutation. Exp Hematol. 2007 ;35(1):32.e1-32.e9.
• 10. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007;110(4):1092–7.
• 11. Zhang S, Qiu H, Fischer BS, Li W, Duan L, Sun X, et al. JAK2 V617F patients with essential thrombocythemia present with clinical features of polycythemia vera. Leuk Lymphoma. 2008;49(4):696-9.
• 12. Karkucak M, Yakut T, Ozkocaman V, Ozkalemkas F, Ali R, Bayram M, et al. Evaluation of the JAK2-V617F gene mutation in Turkish patients with essential thrombocythemia and polycythemia vera. Mol Biol Reports 2012;39(9):8663–7.
• 13. Tefferi A, Lasho TL, Schwager SM, Strand JS, Elliott M, Mesa R, et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 2006;106(3):631–5.
• 14. İlhan G, Karakuş S, Sahin IF. JAK 2V617F Mutation: Frequency and relation to clinical and laboratory features of BCR-ABL negative myeloproliferative diseases. Uluslararası Hematol Derg 2012;22(2):77–84.
• 15. Ünal K, Erdoğan S, Yılmaz FM. JAK 2 V617F gen mutasyon sıklığı ve tam kan sayımı parametreleri ile ilişkisi. Türk Biyokim Derg 2014;39(1):93–8.
• 16. Poopak B, Hagh MF, Saki N, Elahi F, Rezvani H, Khosravipour G, et al. JAK2 V617F mutation in Iranian patients with myeloproliferative neoplasms: clinical and laboratory findings. Turkish J Med Sci 2013;43(3):347–53.
• 17. Singdong R, Siriboonpiputtana T, Chareonsirisuthigul T, Kongruang A, Limsuwanachot N, Sirirat T, et al. Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms. Asian Pac J Cancer Prev 2016;17(10):4647.
• 18. Beutler E. Willams Hematology. 6th ed. New York: McGraw-Hill Medical Pub. Division; 2001. 1357–1408 p.