BCR-ABL negatif kronik myeloproliferatif hastalıkların tanı anındaki genetik analizleri ve bunların klinik etkileri

Year 2020, Volume: 45 Issue: 3, 933 - 939, 30.09.2020

Ayşe Uysal , Şule Altıner Said Çelik Serhat Uysal Alper Han Çebi

https://doi.org/10.17826/cumj.699491

Cited By: 1

Abstract

Amaç: Bu çalışmanın amacı, bcr-abl negatif kronik miyeloproliferatif hastalık tanısı alan hastaların tanı anında JAK2 V617F, kalretikulin (CALR tip-1 ve tip-2) ve MPL-W515K / L mutasyonların sıklığını ve bu mutasyonların klinik önemini tartışmaktır.
Gereç ve Yöntem: Bu çalışmada, Temmuz 2017-Mart 2019 tarihleri arasında BCR-ABL negatif kronik miyeloproliferatif hastalık tanısı alan hastaların demografik özellikleri, tanı alt tipi, risk durumu ve mutasyon analizi araştırılmıştır.
Bulgular: JAK2-V617F mutasyonu 18‘i (% 85,7) polistemia vera (PV) ve geri kalanı (N = 9, %56,2) esansiyel trombositoz (ET) tanısı alan toplam 27 hastada saptandı. ET tanısı konmuş JAK2 V617F negatif 4 (% 57,1) hastada kalretikulin mutasyonu saptandı. Üç hastada CALR-tip 1 mutasyon ve 1 hastada CALR-tip 2 mutasyon tespit edildi. ET tanısı alan hastaların hiçbirinde MPL-W515K / L saptanmadı. Trombotik olay PV' li hastaların % 12,6'sı ve ET' li hastaların% 6,25'i olarak tespit edildi. Hastaların 14'ünde (% 37,8) splenomegali saptandı.
Sonuç: Kronik myeloproliferatif hastalıkların patogenezi, sınıflandırılması ve risk grupları son yıllarda bazı genetik mutasyonların tanımlanması ile iyi karakterize edilmiştir. JAK2 V617F, CALR ve MPL kronik myeloproliferatif hastalıkların patogenezinde, hastalığın tanı, risk sınıflandırması, takipte önemli olan ve kişiselleştirilmiş tıpta önem kazanan aynı zamanda en sık tanımlanan somatik mutasyonlardır.

Keywords

BCR-ABL NEGATİF, JAK2 V617F, kalretikülin, MPL

Supporting Institution

yok

Genetic analysis of BCR-ABL negative chronic myeloproliferative diseases at initial diagnosis and their clinical effects

Abstract

Purpose: The aim of this study to discuss frequency and clinical significance of JAK2-V617F, Calreticulin (CALR type 1 and type-2) and MPL-W515K/L mutations in patients at initial diagnosis of bcr-abl negative chronic myeloproliferative diseases (CMPD).
Materials and Methods: In this study, the demographic characteristics, subtype, risk status and mutation analysis were investigated between July 2017 and March 2019 in patients diagnosed with bcr-abl negative CMPD.
Results: JAK2 V617F mutation was detected in sum of 27 patients, 18 of them (85,7%) diagnosed with polycythemia vera (PV) and rest of them (N=9, 56,2%) diagnosed with essential thrombocytosis (ET). Calreticulin mutation was positive in 4 (57,1%) patients, who were also JAK2 V617F negative, diagnosed with ET. CALR-type 1 mutation was detected in three patients and CALR-type 2 was in one. MPL-W515K/L was not detected in any of patients diagnosed with ET. Thrombotic event was accompanied 12,6% of patients with PV and 6,25% patients with ET. Splenomegaly was noted in 14 (37,8%) of patients. Conclusion: Pathogenesis, classification, and risk groups of CMPD have been well characterized with the identification of some genetic mutations in recent years. JAK2 V617F, CALR and MPL are the most common somatic mutations in the pathogenesis of CMPD, which are important in the diagnosis, risk classification and follow-up of the disease and gain importance in personalized medicine.

Keywords

BCR-ABL negatif, JAK2 V617F, calreticulin, MPL

References

• 1. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5): 937-51.
• 2. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20): 2391-405.
• 3. Hu L, Pu L, Ding Y, Li M, Cabanero M, Xie J, et al. Relationship between JAK2V617F mutation, allele burden and coagulation function in Ph-negative myeloproliferative neoplasms. Hematology. 2017;22(6): 354-60.
• 4. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17): 1779-90.
• 5. Oh ST and Gotlib J JAK2 V617F and beyond: role of genetics and aberrant signaling in the pathogenesis of myeloproliferative neoplasms. Expert Rev Hematol. 2010;3(3): 323-37.
• 6. Chen X, Qi X, Tan Y, Xu Z, Xu A, Zhang L, et al. Detection of MPL exon10 mutations in 103 Chinese patients with JAK2V617F-negative myeloproliferative neoplasms. Blood Cells Mol Dis. 2011;47(1): 67-71.
• 7. Akpinar TS, Hancer VS, Nalcaci M and Diz-Kucukkaya R MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms. Turk J Haematol. 2013;30(1): 8-12.
• 8. Malcovati L, Rumi E and Cazzola M Somatic mutations of calreticulin in myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms. Haematologica. 2014;99(11): 1650-2.
• 9. Wang J, Hao J, He N, Ji C and Ma D The Mutation Profile of Calreticulin in Patients with Myeloproliferative Neoplasms and Acute Leukemia. Turk J Haematol. 2016;33(3): 180-6.
• 10. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25): 2391-405.
• 11. Misawa K, Yasuda H, Araki M, Ochiai T, Morishita S, Shirane S, et al. Mutational subtypes of JAK2 and CALR correlate with different clinical features in Japanese patients with myeloproliferative neoplasms. Int J Hematol. 2018;107(6): 673-80.
• 12. Limsuwanachot N, Rerkamnuaychoke B, Chuncharunee S, Pauwilai T, Singdong R, Rujirachaivej P, et al. Clinical and hematological relevance of JAK2 V617F and CALR mutations in BCR-ABL-negative ET patients. Hematology. 2017;22(10): 599-606.
• 13. Ojeda MJ, Bragos IM, Calvo KL, Williams GM, Carbonell MM and Pratti AF CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms. Hematology. 2018;23(4): 208-11.
• 14. Cabagnols X, Defour JP, Ugo V, Ianotto JC, Mossuz P, Mondet J, et al. Differential association of calreticulin type 1 and type 2 mutations with myelofibrosis and essential thrombocytemia: relevance for disease evolution. Leukemia. 2015;29(1): 249-52.
• 15. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123(10): 1544-51.
• 16. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25): 2379-90.
• 17. Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123(10): 1552-5.
• 18. Chao MP and Gotlib J Two faces of ET: CALR and JAK2. Blood. 2014;123(10): 1438-40.
• 19. Alvarez-Larran A, Pereira A, Guglielmelli P, Hernandez-Boluda JC, Arellano-Rodrigo E, Ferrer-Marin F, et al. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation. Haematologica. 2016;101(8): 926-31.
• 20. Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, Perez-Andreu V, Hernandez-Boluda JC, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116(8): 1205-10; quiz 387.