Remember me
Brief Report
Ngoc N.T.a· Linh N.T.a· Xuan N.T.baUniversity of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam
bInstitute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam
Nguyen Thy Ngoc, nguyen-thy.ngoc@usth.edu.vn
AbstractPurpose: Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations, since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among polycythemia vera patients in Vietnam has not been studied yet. Objectives: The overall study objective was to investigate the frequency of JAK2 exon 12 mutations among V617F-negative polycythemia vera patients in Vietnam. Methods: In this study, the occurrence of these mutations was investigated in a clinical population of 76 Vietnamese polycythemia vera patients by polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing. Results: The result showed that 53 of the patients were V617F-positive, and in 23 V617F-negative patients, only four individuals carried two JAK2 exon 12 mutations. Analysis by different in silico tools predicted that all the two exon 12 mutations detected in this study (JAK2 c.1592A>G; p.H531R and c.1616A>G p.K539R) were benign. Conclusion: These results suggested that the causative mutations in this V617F-negative subgroup might be located in another genetic region, and mutations in exon 12 might not be as common among the V617F-negative polycythemia vera patients as thought.
© 2022 The Author(s). Published by S. Karger AG, Basel
References Bose P, Verstovsek S. Updates in the management of polycythemia vera and essential thrombocythemia. Ther Adv Hematol. 2019;10:2040620719870052. Tefferi A. Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014;89(9):915–925. Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87(3):285–93. Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010;24(6):1128–38. 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. Schaub FX, Looser R, Li S, Hao-Shen H, Lehmann T, Tichelli A, et al. Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood. 2010;115(10):2003–7. Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129(6):667–79. Leszczynska A, Grzenkowicz-Wydra J, Chmielewska-Gorycka L, Bieniaszewska M, Hellmann A. Detection of JAK2 exon 12 mutations in JAK2 V617F-negative polycythemia vera patients by cloning technique. Acta Haematol. 2016;136(2):123–8. Yeh YM, Chen YL, Cheng HY, Su WC, Chow NH, Chen TY, et al. High percentage of JAK2 exon 12 mutation in Asian patients with polycythemia vera. Am J Clin Pathol. 2010;134(2):266–70. Choi Y, Chan AP. PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics. 2015;31(16):2745–7. Bendl J, Musil M, Stourac J, Zendulka J, Damborsky J, Brezovsky J. PredictSNP2: a unified platform for accurately evaluating SNP effects by exploiting the different characteristics of variants in distinct genomic Regionsregions. PLoS Comput Biol. 2016;12(5):e1004962. Capriotti E, Fariselli P. PhD-SNPg: a webserver and lightweight tool for scoring single nucleotide variants. Nucleic Acids Res. 2017;45(W1):W247–52. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073–81. Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013;Chapter 7:Unit7.20. 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. Maddali M, Kulkarni UP, Ravindra N, Jajodia E, Arunachalam AK, Suresh H, et al. JAK2 exon 12 mutations in cases with JAK2V617F-negative polycythemia vera and primary myelofibrosis. Ann Hematol. 2020;99(5):983–9. Article / Publication DetailsFirst-Page Preview
Received: May 01, 2022
Accepted: July 22, 2022
Published online: August 03, 2022
Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 1
ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)
For additional information: https://www.karger.com/HHE
Figures
Tables
Open Access License / Drug Dosage / Disclaimer
This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Comments (0)