The Frequency of JAK2 V617F Mutation in Patients with Chronic Myeloproliferative Disease

Abstract

Background: Chronic myeloproliferative diseases are characterized by excessive proliferation of blood cell lines, the most common of which are polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), usually JAK2 (Janus kinase 2), CALR (calreticulin) and MPL (myeloproliferative leukemia) genes occur as a result of specific somatic mutations. The aim of this study was to determine the frequency of JAK2 V617F mutation in PV, ET and PMF patients who applied to the genetic polyclinic due to polycythemia and to compare these results with the literature data.

Methods: The laboratory results of 267 patients who presented with polycythemia between February 2017-February 2019 and tested JAK2 V617F mutation analysis were retrospectively reviewed. The patients were divided into three groups as PV, ET and PMF. The frequency of JAK2 V617F mutation and demographic data were recorded in each group.

Results: Of 267 patients included in the study, 235 (88%) had PV, 31 (11.6%) had ET and 1 (0.4%) had PMF. JAK2 V617F mutation positivity was detected in 8.5% of PV patients and 9.7% of ET patients. The JAK2 V617F mutation was significantly higher in Syrian patients than in Turkish patients when compared to those of origin (p <0.05).

Conclusions: In this study, a significant difference was found between Turkish and Syrian citizens in terms of JAK2 V617F mutation. This suggests that the JAK2 V617F mutation may differ by origin. In addition, this study is important because it is the first study to evaluate the frequency of JAK2 V617F mutation in Şanlıurfa.

Kronik Miyeloproliferatif Hastalık Olgularında JAK2 V617F Mutasyon Sıklığı

Abstract

Amaç: Kronik miyeloproliferatif hastalıklar kan hücre serilerinin aşırı proliferasyonu ile karakterize olup bu hastalıklardan sıklıkla görülen polisitemiavera (PV), esansiyeltrombositemi (ET) ve primermiyelofibrozis (PMF) genellikle JAK2 (Januskinaz 2), CALR (calreticulin) ve MPL (myeloproliferativeleukemia) genlerinde spesifik somatik mutasyonlar sonucu ortaya çıkmaktadır. Bu çalışmada polisitemi nedeniyle genetik polikliniğine başvuran PV, ET ve PMF hastalarında JAK2 V617F mutasyon sıklığının hastalık gruplarına göre tespiti ve elde edilen bu sonuçların literatür verileri ile karşılaştırılması amaçlanmıştır.

Materyal ve Metod: Şubat 2017-Şubat 2019 tarihleri arasında polisitemi nedeniyle başvuran ve JAK2 V617F mutasyon analizi yapılan 267 hastanın laboratuvar sonuçları retrospektif olarak incelendi. Hastalar PV, ET ve PMF tanısı alanlar olmak üzere 3 gruba ayrıldı. Her grupta JAK2 V617F mutasyon sıklığı ve hastaların demografik verileri kaydedildi.

Bulgular: Çalışmaya alınan toplam 267 hastanın 235’inde (%88) PV, 31’inde (%11,6) ET ve 1 hastada (%0,4) PMF tanısı vardı. JAK2 V617F mutasyon pozitifliği PV hasta grubunun %8,5’nde, ET hasta grubunun %9,7’sinde saptandı. JAK2 V617F mutasyonu gözlenme durumu kökenlere göre karşılaştırıldığında Suriye’li hastalarda Türk hastalara kıyasla anlamlı olarak daha yüksekti (p <0.05).

Sonuç: Bizim çalışmamızda Türk ve Suriye vatandaşları arasında JAK2 V617F mutasyonu açısından anlamlı farklılık tespit edildi. Bu durum JAK2 V617F mutasyonunun kökenlere göre farklılık gösterebileceğini göstermektedir. Ayrıca bu çalışma Şanlıurfa ilinde JAK2 V617F mutasyon sıklığının değerlendirildiği ilk çalışma olması nedeniyle önem arz etmektedir.

Keywords

• JAK2 V617F mutasyonu,polisitemi,polistemia vera,esansiyel trombositemi,primer miyelofibrozis

References

1. 1. Michiels, J.J., et al., Changing concepts of diagnostic criteria of myeloproliferative disorders and the molecular etiology and classification of myeloproliferative neoplasms: from Dameshek 1950 to Vainchenker 2005 and beyond. Acta haematologica, 2015. 133(1): p. 36-51.
2. 2. Arber, D.A., et al., The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016. 127(20): p. 2391-2405.
3. 3. Baxter, E.J., et al., Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. The Lancet, 2005. 365(9464): p. 1054-1061.
4. 4. Kaushansky, K., The chronic myeloproliferative disorders and mutation of JAK2: Dameshek's 54 year old speculation comes of age. Best Practice & Research Clinical Haematology, 2007. 20(1): p. 5-12.
5. 5. Jones, A.V., et al., JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nature genetics, 2009. 41(4): p. 446.
6. 6. Wadleigh, M. and A. Tefferi, Classification and diagnosis of myeloproliferative neoplasms according to the 2008 World Health Organization criteria. International journal of hematology, 2010. 91(2): p. 174-179.
7. 7. Jones, A.V., et al., Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood, 2005. 106(6): p. 2162-2168.
8. 8. Kralovics, R. and R.C. Skoda, Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood reviews, 2005. 19(1): p. 1-13.

9. 9. Maffioli, M., E. Orlandi, and F. Passamonti, Chronic myeloproliferative neoplasms in the elderly. European journal of internal medicine, 2018. 58: p. 33-42.
10. 10. Tefferi, A., et al., The clinical phenotype of wild‐type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer: Interdisciplinary International Journal of the American Cancer Society, 2006. 106(3): p. 631-635.
11. 11. Najean, Y., J. Rain, and C. Billotey, Epidemiological data in polycythaemia vera: a study of 842 cases. Hematology and cell therapy, 1998. 40(4): p. 159-165.
12. 12. Chaiter, Y., et al., High incidence of myeloproliferative disorders in Ashkenazi Jews in northern Israel. Leukemia & lymphoma, 1992. 7(3): p. 251-255.
13. 13. Schnittger, S., et al., Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera. haematologica, 2009. 94(3): p. 414-418.