Correlation of Thrombosis and Clinicohematological Parameters with JAK2V617F Mutation in Philadelphia-Negative CMPNs: A Study from India

Abstract

Objective Philadelphia-negative chronic myeloproliferative neoplasms (CMPNs), which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by the presence of JAK2V617F (exon 14) mutation, and this occurs in 90 to 95% cases of PV and 50 to 60% cases of ET and PMF. Still, this is a matter of debate regarding the correlation of this mutation with thrombosis and clinicohematological parameters in CMPNs. So, we conducted this study to ascertain the association of JAK2V617F mutation with thrombotic complications and clinicohematological parameters of these patients.

Materials and Methods This prospective and retrospective study was conducted during 2018 to 2019 at the Department of Laboratory Sciences and Molecular Medicine of a tertiary care hospital, and 160 CMPN patients were enrolled. Complete hemogram was done and DNA was extracted, followed by real-time qualitative polymerase chain reaction to check for JAK2V617F mutation. This mutation was then correlated with complications, mainly thrombosis, hematological parameters, and clinical parameters such as age and splenomegaly.

Results Among 160 CMPN patients, 60 were females and 100 were males, with male to female ratio of 1:0.6, and age range of 27 to 85 years. Total 91 (56.9%) patients were JAK2V617F positive and the remaining 69 (43.1%) were negative for this mutation. We observed statistically significant correlation of leukocyte count, splenomegaly, and thrombosis in JAK2V617F-mutated patients as compared to unmutated patients.

Conclusion This study emphasizes the importance of JAK2V617F mutation in CMPNs and stresses on its association with clinical, hematological phenotype, and thrombotic complications, which may open new horizons in prognostication and management protocol.

Keywords

JAK2V617F mutation - Philadelphia-negative CMPNs - thrombosis

Publikationsverlauf

Artikel online veröffentlicht:
20. Oktober 2022

• References

• 1 Gari M, Al-Sayes F, Ahmed F. et al. JAK2 mutations in chronic myeloproliferative neoplasm; towards the application of personalized treatments for Saudi patients. Open Journal of Blood Diseases 2012; 2: 17-21
• 2 Singh K, Sazawal S, Chhikara S, Mahapatra M, Saxena R. Association of JAK2V617F mutation with thrombosis in Indian patients with Philadelphia negative chronic myeloproliferative neoplasms. Indian J Pathol Microbiol 2018; 61 (03) 371-374
• 3 de Freitas RM, Santos MdeO, Maranduba CM. The JAK2 gene as a protagonist in chronic myeloproliferative neoplasms. Rev Bras Hematol Hemoter 2013; 35 (04) 278-279
• 4 Barbui T, Finazzi G, Falanga A. Myeloproliferative neoplasms and thrombosis. Blood 2013; 122 (13) 2176-2184
• 5 Grinfeld J, Nangalia J, Green AR. Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms. Haematologica 2017; 102 (01) 7-17
• 6 Uyanik MS, Baysal M, Pamuk GE. et al. Is JAK2V617F mutation the only factor for thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms?. Indian J Hematol Blood Transfus 2016; 32 (03) 262-267
• 7 Vannucchi AM. JAK2 mutation and thrombosis in the myeloproliferative neoplasms. Curr Hematol Malig Rep 2010; 5: 22-28
• 8 Dentali F, Squizzato A, Appio L, Brivio L, Ageno W. JAK2V617F mutation in patients with arterial thrombosis in the absence of overt myeloproliferative disease. J Thromb Haemost 2009; 7 (04) 722-725
• 9 Ar MC, Hatemi G, Ekizoğlu S. et al. JAK2 (V617F) mutation is not associated with thrombosis in Behcet syndrome. Clin Appl Thromb Hemost 2012; 18 (04) 421-426
• 10 Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 2011; 29 (05) 573-582
• 11 Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc 2006; 81 (02) 159-166
• 12 Sazawal S, Singh K, Chhikara S, Chaubey R, Mahapatra M, Saxena R. Influence of JAK2V617F allele burden on clinical phenotype of polycythemia vera patients: a study from India. South Asian J Cancer 2019; 8 (02) 127-129
• 13 Arber DA, Orazi A, Hasserjian R. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127 (20) 2391-2405
• 14 Cetin G, Ozkan T, Turgut S. et al. Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis. Mol Biol Rep 2014; 41 (10) 6737-6742
• 15 Kralovics R, Passamonti F, Buser AS. et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352 (17) 1779-1790
• 16 Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C. The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol 2006; 132 (02) 244-245
• 17 Ohyashiki K, Ito Y, Hori K. et al. Thrombosis can occur at any phase of essential thrombocythemia with JAK2(V617F) mutation: a single institutional study in Japan. Leukemia 2007; 21: 1570-1571
• 18 Ayer M, Menken İ, Yamak M, Ayer FA, Kırkızlar O, Aktuğlu BM. The impact of mean platelet volume (MPV) and JAK-2 mutation on thrombosis in chronic myeloproliferative diseases. Indian J Hematol Blood Transfus 2017; 33: 181-187
• 19 Zhao S, Zhang X, Xu Y. et al. Impact of JAK2V617F mutation burden on disease phenotype in Chinese patients with JAK2V617F-positive polycythemiavera (PV) and essential thrombocythemia (ET). Int J Med Sci 2016; 13: 85-91