PREVALENCE OF MUTATIONS IN JAK2 AMONG BLOOD DONORS
https://doi.org/10.25837/HAT.2018.49..1..006
Abstract
We present the results of testing 1231 venous blood samples from 1150 blood donors for V617F somatic mutation in the JAK2 gene. The tests were performed using allele-specific real-time polymerase chain reaction in pooled venous blood samples. The mutation was found in 8 (0.65%) samples from 5 men aged 31—52 years. The allelic load of the mutant gene was 0.07—2.6%. Four of the five mutation carriers had been donors for 7.5—13 years and had made 16 to 90 donations each. Only one of the five men had developed hematological changes characteristic of polycythemia that caused to refrain him from donations. Ability of the mutant clones to form the erythropoietin-independent colonies in vitro and generate foci of extramedullary proliferation raises the concern about safety of blood transfusions and bone marrow transplantations from donors carrying the JAK2 V617F mutation. Whether the frequency of blood donations increases the risk of somatic mutations in JAK2 is a question that requires further studies.
Supporting agencies: The study was supported financially by the Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences and by the Siberian Federal University. Additional financing was received from the Krasnoyarsk Regional Association of Medical Diagnostic Laboratories.
About the Authors
I. A. Olkhovskiy
Krasnoyarsk branch of the National Research Center of Hematology; Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
Russian Federation
Olkhovskiy Igor A., MD, PhD, associate professor, director of Krasnoyarsk Branch of the National Research Center for Hematology, senior researcher of the Krasnoyarsk Scientific Center of Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
Russian Federation
Olkhovskiy Igor A., MD, PhD, associate professor, director of Krasnoyarsk Branch of the National Research Center for Hematology, senior researcher of the Krasnoyarsk Scientific Center of Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk
N. G. Filina
Krasnoyarsk Regional Blood Center № 1; Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk
Russian Federation
Russian Federation
A. S. Gorbenko
Krasnoyarsk branch of the National Research Center of Hematology, Krasnoyarsk
Russian Federation
Russian Federation
M. A. Stolyar
Krasnoyarsk branch of the National Research Center of Hematology; Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences; Siberian Federal University, Krasnoyarsk
Russian Federation
Russian Federation
T. B. Kolotvina
Krasnoyarsk Regional Blood Center № 1, Krasnoyarsk
Russian Federation
Russian Federation
T. N. Subbotina
Krasnoyarsk branch of the National Research Center of Hematology; Siberian Federal University, Krasnoyarsk
Russian Federation
Russian Federation
References
1. Jelinek J, Oki Y, Gharibyan V et al. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 2005; 106:3370—3373.
2. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008; 22:14—22.
3. Xu X, Zhang Q, Luo J et al. JAK2V617F: prevalence in a large Chinese hospital population. Blood 2007; 109:339—342.
4. Orloff K, Tierney B. Community Health Screening Report, 2010. Доступно в интернете по адресу: http://www.atsdr.cdc.gov/HAC/pha/CommunityHealthScreeninginPA2010/CommunityHealthScreeningReport.pdf (по состоянию на25 июня2016 г.).
5. Nielsen C, Bojesen SE, Nordestgaard BG et al. JAK2 V617F somatic mutation in the general population: myeloproliferative neoplasm development and progression rate. Haematologica 2014; 99:1448—1455.
6. Titmarsh GJ, Duncombe AS, McMullin MF et al. How common are myeloproliferative neoplasms? A systematic review and meta-analysis. Am J Hematol 2014: 89:581—587.
7. Ольховский И. А., Столяр М. А. Особенности агрегационной активности тромбоцитов у пациентов с мутацией в генеJAK2: гендерные отличия и эффект аспирина. Гематология и трансфузиология2014; 59:11—14.
8. Schwarz J, International Hematology Expert Meeting 2014 Hermagor/ Austria. Доступно в интернете по адресу: http://xn-80aajeesum3a.xn-p1ai/pdf/Myeloproliferative.pdf (по состоянию на25 июня2016 г.).
9. Dentali F, Ageno W, Rumi E et al. Cerebral venous thrombosis and myeloproliferative neoplasms: results from two large databases. Thromb Res 2014; 134:41—43.
10. Passamonti SM, Biguzzi E, Cazzola M et al. The JAK2 V617F mutation in patients with cerebral venous thrombosis. J Thromb Haemost 2012; 10:998—1003.
11. Xavier SG, Gadelha T, Rezende SM et al. JAK2V617F mutation in patients with thrombosis: to screen or not to screen? Int J Lab Hematol 2011; 33:117—124.
12. Smalberg JH, Arends LR, Valla DC et al. Myeloproliferative neoplasms in Budd—Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood 2012; 120:4921—4928.
13. Ольховский И. А., Карапетян Г. Э., Горбенко А. С. и др. Выявляемость пациентов с онкогенной соматической мутацией янускиназы-2 (V617F JAK2) в рамках программ диспансерного и профилактического осмотров. Клиническая лабораторная диагностика2016; 61:275—278.
14. Muendlein A, Gasser K, Kinz E et al. Evaluation of the prevalence and prospective clinical impact of the JAK2 V617F mutation in coronary patients. Am J Hematol 2014; 89:295—301.
15. Hinds DA, Barnholt KE, Mesa RA et al. Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms. Blood 2016; 128:1121—1128.
16. Vassiliou GS. JAK2 V617F clonal disorders: fate or chance? Blood 2016; 128:1032—1033.
17. Sidon P, El Housni H, Dessars B et al. The JAK2V617F mutation is detectable at very low level in peripheral blood of healthy donors. Leukemia 2006; 20:1622.
18. Tagariello G, Di Gaetano R, Sartori R et al. The JAK2V617F tyrosine kinase mutation in blood donors with upper-limit haematocrit levels. Blood Transfusion 2009; 7:111—116.
19. Magnussen K, Hasselbalch H, Ullum H et al. Characterization of blood donors with high haemoglobin concentration. Vox Sang 2013; 104:110—114.
20. Edgren G, Reilly M, Hjalgrim H et al. Donation frequency, iron loss, and risk of cancer among blood donors. J Natl Cancer Inst 2008; 100:572—579.
21. Edgren G, Nyren O, Hultcrantz M et al. Blood donation and risk of polycythemia vera. Transfusion 2016; 56:1622—1627.
22. Khudhair MA. Detection of JAK2V617F mutation and estimation of serum erythropoietin among blood donors with high hematocrit. University of Baghdad, 2014. Доступно в интернете по адресуhttp://www.comed.uobaghdad.edu.iq/uploads/Thesis%202015/May%20Ahmed%20 Khudhair.pdf (по состоянию на25 мая2016 г.).
23. Горбенко А. С., Столяр М. А., Субботина Т. Н. и др. Разработка метода определения аллельной нагрузки соматической мутацииV617F в генеJAK2 (янускиназы2) в пулах проб венозной крови. Лабораторная служба2016; 1:19—25.
24. Krichevsky S, Prus E, Perlman R et al. The JAK2V617F mutation in normal individuals takes place in differentiating cells. Blood Cells Mol Dis 2017; 63:45—51.
25. Nemer W, De Grandis M, Brusson M. Abnormal adhesion of red blood cells in polycythemia vera: a prothrombotic effect? Thromb Res 2014; 133:S107—111.
26. Kubota Y, Tanaka T, Ohnishi H et al. Constitutively activated phosphatidylinositol 3-kinase primes platelets from patients with chronic myelogenous leukemia for thrombopoietin-induced aggregation. Leukemia 2004; 18:1127—1137.
27. Falanga A, Marchetti M, Vignoli A et al. Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera. Exp Hematol 2005; 33:523—530.
28. Falanga A, Marchetti M. Thrombotic disease in the myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program 2012; 2012:571—581.
29. Hirsch P, Mamez AC, Belhocine R et al. Clonal history of a cord blood donor cell leukemia with prenatal somatic JAK2 V617F mutation. Leukemia 2016; 30:1756—1759.
Review
For citations:
Olkhovskiy I.A., Filina N.G., Gorbenko A.S., Stolyar M.A., Kolotvina T.B., Subbotina T.N. PREVALENCE OF MUTATIONS IN JAK2 AMONG BLOOD DONORS. Russian journal of hematology and transfusiology. 2018;63(1):65-70. (In Russ.) https://doi.org/10.25837/HAT.2018.49..1..006
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