Genetic Profile of Patients with Classical Ph-negative Chronic Myeloproliferative Diseases in the Republic of Sakha (Yakutia)

ORIGINAL ARTICLE
Tuiara N. Aleksandrova, Nadezhda I. Pavlova, Khariton A. Kurtanov, Inna I. Mulina, Vera N. Yadrikinskaya, Lena D. Terekhova, Irina E. Solovieva, Aleksandra T. Diakonova, Natalia A. Solovyeva

 
International Journal of Biomedicine. 2020;10(1):54-57.
DOI: 10.21103/Article10(1)_OA8
Originally published March 15, 2020

Abstract: 

Background: Mutations in the JAK2, CALR, and MPL genes are key factors of the classical Ph-negative CMPD pathogenesis with demonstrated diagnostic and prognostic value. The aim of this research was to study the prevalence of JAK2, CALR, and MPL mutations in patients with CMPD and healthy individuals in the Republic of Sakha (Yakutia) (RS(Y)).
Methods and Results: The study included patients with previously confirmed diagnoses of PV (n=15), ET (n=16), and PMF (n=11) and 68 people with peripheral blood changes, suspected to have CMPD. The control group included 184 healthy volunteers. All patients and participants in the control group were genotyped according to the following SNPs: the JAK2 rs77375493 SNP, the CALR rs765476509 SNP, the CALR rs1450785140 SNP, the MPL rs121913616 SNP, and the MPL rs121913615.
The prevalence of the JAK2V617F mutation among PV patients in the RS(Y) was 90.9%. Patients with ET in 61.3% of cases were carriers of the JAK2V617F mutation, in 6.4% of CALR mutations, and in 3.2% of the MPLW515L mutations. In PMF patients, the JAK2V617F mutation was detected in 64.7% of cases, and the Type 1 CALR mutation was detected in 17.6% of cases. Carriage of the JAK2V617F mutation was revealed in 1.1% of healthy individuals and in 4.4% of individuals with initial signs of a myeloproliferative process.
Conclusion: Early molecular genetic testing will improve the timely diagnosis of CMPD and possibly reduce the number of complications.

Keywords: 
chronic myeloproliferative diseases • gene • mutations • single nucleotide polymorphism
References: 
  1. De Freitas RM, da Costa Maranduba CM. Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview. Rev Bras Hematol Hemoter. 2015;37(5):348-53. doi:10.1016/j.bjhh.2014.10.001.
  2. Langabeer SE, Andrikovics H, Asp J, Bellosillo B, Carillo S, Haslam K, et al.; MPN&MPNr-EuroNet. Molecular diagnostic of myeloproliferative neoplasms. Eur J Haematol. 2015;95(4):270-9. doi: 10.1111/ejh.12578.
  3. Silyutina AA, Gin II, Matyukhina NM, Balayan EN, Butylin PA. [Myelofibrosis Models: Literature Review and Own Data]. Clinical Oncohematology. 2017;10(1):75–84 doi: 10.21320/2500-2139-2017-10-1-75-84. [Article in Russian].
  4. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowith 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):2391-2405.
  5. Melikyan AL, Subortseva IN. [Biology of myeloproliferative malignancies]. Clinical Oncohematology. 2016;9(3):314–25. doi: 10.21320/2500-2139-2016-9-3-314-325. [Article in Russian].
  6. Shikhbabaeva DI, Polushkina LB, Shuvaev VA, Martynkevich IS, Kapustin SI, Zamotina TB, et al. Genetic markers of hereditary thrombophilia and risk of thrombotic complications in patients with polycythemia vera. Clinical Oncohematology. 2017;10(1):85-92. doi: 10.21320/2500-2139-2017-10-1-85-92. [Article in Russian].
  7. Olkhovskiy IA, Filina NG, Gorbenko AS, Stolyar MA, Kolotvina TB, Subbotina TN. [Prevalence of mutations in JAK2 among blood donors]. Russian Journal of Hematology and Transfusiology. 2018;63(1):65-70. doi: 10.25837/HAT.2018.49..1..006. [Article in  Russian].
  8. Cordua S, Kjaer L, Skov V, Pallisgaard N, Hasselbalch HC, Ellervik C. Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population. Blood. 2019;134(5):469-479. doi: 10.1182/blood.2019002756
  9. Shepard GC, Lawson HL, Hawkins GA, Owen J. BsaXI/RFLP analysis of initial or selectively reamplified PCR product is unreliable in detecting the V617F mutation in JAK2. Int J Lab Hematol. 2010;33(3):267-71. doi: 10.1111/j.1751-553X.2010.01282.x
  10. Jeong JH, Te Lee H, Seo JY, Seo YH, Kim KH, Kim MJ. Screening PCR Versus Sanger Sequencing: Detection of CALR Mutations in Patients With Thrombocytosis. Ann Lab Med. 2016;36(4):291-9. doi: 10.3343%2Falm.2016.36.4.291
  11. Chi J, Pierides Ch, Mitsidou A, Miltiadou A, Gerasimou P, Nicolaou K et al. A sensitive detection method for MPLW515L or MPLW515K mutation in myeloproliferative disorders. European Journal of Experimental Biology. 2014;4(5):33-36.
  12. Silvennoinen O, Hubbard SR. Molecular insights into regulation of JAK2 in myeloproliferative neoplasms. Blood. 2015;125(22):3388-92. doi: 10.1182/blood-2015-01-621110
  13. Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017;129(6):680-692. doi: 10.1182/blood-2016-10-695957
  14. Nielsen C, Birgens HS, Nordestgaard BG, Bojesen SE. Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in 49 488 individuals from the general population. Br J Haematol. 2013;160(1):70-9. doi: 10.1111/bjh.12099
  15. Nielsen C, Birgens HS, Nordestgaard BG, Kjaer L, Bojesen SE. The JAK2 V617F somatic mutation, mortality and cancer risk in the general population. Haematologica. 2011;96(3):450-3. doi: 10.3324/haematol.2010.033191.

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Received January 20, 2020.
Accepted March 6, 2020.
©2020 International Medical Research and Development Corporation.