JAK2 V617F MUTATION STATUS AND ALLELE BURDEN IN SUDANESE PATIENTS WITH CHRONIC MYELOPROLIFERATIVE NEOPLASMS

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  • Submited: January 28, 2016
  • Published: June 16, 2017

Abstract

Background: The JAK2 V617F mutation is frequent in the majority patients with myeloproliferative neoplasms. The published studies regarding the impact of JAK2 V617F allele burden on phenotypic properties in PV, ET and pri­mary myelofibrosis have reported variable results. The aim of this study was to determine the JAK2 V617F allele burden. Furthermore, we examined the association of quantitative JAK2 V617F allele burden with laboratory characteristics and clinical phenotype in Sudanese patients diagnosed with chronic myeloproliferative neoplasms. 

Methods: The study was conducted from 2013 to 2015. Peripheral blood samples of 259 patients with MPNs were involved: 159 with Polycythemia Vera, 55 with Essential Thrombocytosis and 45 with Primary Myelofibrosis. Allele specific polymerase chain reaction  was used to screen the JAK2 V617F, and The quantitative real-time polymerase chain reaction (qRT-PCR) technology (Ipsogen JAK2 Muta Quant Kit, Germany) was used to determinate the percentage of mutated alleles in genomic DNA among JAK2 V617F positive MPNs. Laboratory and clinical parameters were obtained from patient's medical records.

Results: The JAK2 V617F mutation was detected in 81.7%, 56.4%, and 51.1% of polycythemia vera, essential thrombocythemia, and primary myelofibrosis patients, respectively. The mean allele burden of JAK2 V617F for positive myeloproliferative neoplasms was (69.3% ± 32.8) in MF, (60.2% ± 33.4) in polycythemia vera and (31.5% ± 31.1) in essential thrombocythemia. The prevalence of JAK2 V617F mutation with high allele burden (i.e. mutant allele burden exceeded 50% relative to wild type) was 85 (53.4 %) of 159 in polycythemia vera patients, 7 (12.7%) of 55 essential thrombocythemia patients and 14 (31.1%) of 45 primary myelofibrosis patients. JAK2 V617F allele burden was correlate of with high white blodd cells in in polycythemia vera (p?=?.006), and lower platelet count in PV (p?=?.000) and primary myelofibrosis (p?=?.015).

Conclusion:The allele burden of JAK2 V617F was significantly different significantly among MPNs subgroups(PV, ET and PMF).

Key words: JAK2 V617F mutation, Sudanese Patients, Chronic Myeloproliferative Neoplasm

 

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References

  1. Edward P.Gelmann, Charles L.Sawyes, Frankj. Rauscher. Molecular Oncology: Causes of cancer and targets for treatment. Cambridge, 2014, P818
  2. Amy V. Jones, Nicholas C. P. Cross. Inherited predisposition to myeloproliferative neoplasms. Ther Adv Hematol, 2013;4(4) 237–53
  3. Dan Jones, Cameron Yin. Neoplastic hematopathology: Experimental and Clinical Approaches. 2010, P177
  4. Tefferi, A.; Vardiman, J.W. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008, 22(1):14-22
  5. Baxter, E., Scott, L., Campbell, P., East, C., Fourouclas, N., Swanton, S. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054–61
  6. Kralovics, R., Passamonti, F., Buser, A., Teo, S., Tiedt, R., Passweg, J. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779–90
  7. Ross L. Non CML myeloproliferative neoplasms. Hematology/oncology clinics of North America. October 2012. Volume 26. Number 5
  8. James C., Ugo V., Le Couedic J., Staerk, J., Delhommeau, F., Lacout, C. A unique Clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature;2005,434:1144-8
  9. Ipek Yonal-Hindilerden, Aynur Daglar-Aday, Basak Akadam-Teker, Ceylan Yilmaz, Meliha Nalcaci, Akif Selim Yavuz, Deniz Sargin J Clin. The Burden of JAK2 V617F Mutated Allele in Turkish Patients with Myeloproliferative Neoplasms. Med Res 2015;7(3):161–70
  10. Rajnai H, Bodor C, Reiniger L, Timár B, Csernus B, Szepesi A, Csomor J, Matolcsy A. Novel method in diagnosis of chronic myeloproliferative disorders--detection of JAK2 mutation. Orv Hetil 2006;147(45):2175-9
  11. Duletic AN, Dekanic A, Hadzisejdic I, Kusen I, Matusan llijas K, Grohovac D, Grahovac B, Jonjic N. JAK2 V617F mutation is associated with clinical and laboratory features of myeloproliferative neoplasms. Coll Antropol 2012; 36(3):859-65
  12. Ha J-S, Kim Y-K, Jung S-I, Jung H-R, Chung I-S. Correlations between Janus Kinase 2 V617F Allele Burdens and Clinicohematologic Parameters in Myeloproliferative Neoplasms. Annals of Laboratory Medicine. 2012;32(6):385-91. doi:10.3343/alm.2012.32.6.385
  13. Delhommeau F, Jeziorowska D, Marzac C, Casadevall N. Molecular aspects of myeloproliferative neoplasms. Int J Hematol 2010;91:165–73
  14. Zhu JF, Liu Y, Liu P, Jia MF, Cheng J, Zhao L. Zhongguo Shi Yan Xue Ye Xue Za Zhi. JAK2 V617F mutation in the patients with myeloproliferative disorder and its relation with clinical characteristics. 2011;19(4):916-20, Chinese PMID 21867614
  15. Benmoussa A, Dehbi H, Fehri S, Quessar A, Nadifi S. JAK2 V617F mutation in Moroccan patients with myeloproliferative disorders: contribution, diagnosis and therapeutic prospects. Pathol Biol (Paris). 2011 Aug;59(4):e89-92. doi: 10.1016/j.patbio.2009.06.005. Epub 2009 Nov 24
  16. Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP, Li CY, Wu W, Ketterling RP, Pardanani A, Tefferi A. Clinical correlates of JAK2 V617F allele burden in essential thrombocythemia. Cancer. 2007;109(11):2279-84
  17. Payzin KB, Savasoglu K, Alacacioglu I, Ozdemirkiran F, Mutlu BB, Bener S, Calli AO, Kucukzeybek BB, Aksun S. JAK2 V617F mutation status of 232 patients diagnosed with chronic myeloproliferative neoplasms. Clin Lymphoma Myeloma Leuk. 2014 Dec;14(6):525-33. doi: 10.1016/j.clml.2014.02.013. Epub 2014 Mar 5
  18. Hamidah NH, Farisah NR, Azlinda AB, Wong FL, Das S, Fadillah SA, Ainoon O. A study of JAK2 (V617F) gene mutation in patients with chronic myeloproliferative disorders Clin Ter. 2012;163(2):109-13
  19. Sang Hyuk Park, Hyun-Sook Chi, and Chan-Jeoung Park. The allele burden of JAK2 V617F can aid in differential diagnosis of Philadelphia Chromosome-Negative Myeloproliferative Neoplasm. Blood Res 2013;48(2): 128–32.
  20. Francesco Passamonti, Elisa Rumi. Clinical relevance of JAK2 (V617F) mutant allele burden. Haematol. 2008.001271 doi: 10.3324
  21. Ross L. Levine. JAK2 V617F: you can’t have too much blood 2008 111: 3913doi:10.1182/blood-2008-01-133322
  22. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–97
  23. Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R et al. Clinical profile of homozygous JAK2 V617F mutation in patients with polycythemia vera or essential thrombocythemia. Blood 2007; 110: 840–46
  24. Tefferi A, Lasho TL, Schwager SM, et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2(V617F) in polycythemia vera. Cancer 2006;106:631-35
  25. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-790
  26. Ha JS, Kim YK, Jung SI, Jung HR, Chung IS. Correlations between Janus Kinase 2 V617F Allele Burdens and Clinicohematologic Parameters in Myeloproliferative Neoplasms. Ann Lab Med. 2012 Nov;32(6):385-91. doi: 10.3343/alm.2012.32.6.385. Epub 2012 Oct 17
  27. Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, et al. Prospective identifica tion of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia. 2007;21:1952–59
  28. Larsen TS, Pallisgaard N, Møller MB, Hasselbalch HC. The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis--impact on disease phenotype. Eur J Haematol. 2007 Dec; 79(6):508-15. Epub 2007 Oct 23
  29. Yonal I, Daglar Aday A, Akadam Teker B, et al. Impact of JAK2 V617F Mutational Status on Phenotypic Features in Essential Thrombocythemia and Primary Myelofibrosis. Turk J Haematol. 2015 Apr 27; Epub 2015 Apr 27
  30. Singh N, Sazawal S, Upadhyay A, Chhikara S, Mahapatra M, Saxena R. Correlation of JAK2 V617F mutational status in primary myelofibrosis with clinico-hematologic characteristics and international prognostic scoring system scoring: a single center experience. Indian J Pathol Microbiol. 2015 Apr-June; 58(2):187-91. doi: 10.4103/0377-4929.155311
  31. Alshemmari SH, Rajaan R, Ameen R, Al-Drees MA, Almosailleakh MR. JAK2 V617F allele burden in patients with myeloproliferative neoplasms. Ann Hematol. 2014 May;93(5):791-6. doi: 10.1007/s00277-013-1988-6. Epub 2013 Dec 22
  32. Antonioli E, Guglielmelli P, Poli G, et al. Influence of JAK2 V617F allele burden on phenotype in essential thrombocythemia. Haematologica. 2008;93(1):41–8. doi: 10.3324/haematol.11653
How to Cite
Abkar, H., Hassan, F., & Mohamed, B. (2017). JAK2 V617F MUTATION STATUS AND ALLELE BURDEN IN SUDANESE PATIENTS WITH CHRONIC MYELOPROLIFERATIVE NEOPLASMS. Ethiopian Medical Journal, 55(3). Retrieved from https://emjema.org/index.php/EMJ/article/view/307

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