Volume 9, Issue 2 (Vol.9 No.2 Jul 2020)
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Pardis Clinical and Genetics Laboratory, Mashhad, Iran & Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, MUMS, Mashhad, Iran
Abstract: (5029 Views)
Background: Janus kinase 2 (JAK2) is a tyrosine kinase located in the cytoplasm that plays a critical role in the signal transduction of cytokines and growth hormones. The conversion of valine to phenylalanine at the polypeptide position 617 results in the JAK2 (V617F) mutation, which often found in patients with myeloproliferative neoplasms (MPNs). As a result of this mutation, JAK2 is constitutively activated leading to uncontrolled cell growth. The present study aimed to investigate the frequency and relationship of the JAK2 (V617F) mutation in a population of patients with MPNs in Iran.
Methods: A total of 213 patients with myeloproliferative diseases (MPDs), were included in the study. Real-time PCR was used to detect the presence of the JAK2 (V617F) mutation in the genomic DNA isolated from patient peripheral blood samples.
Results: Of the 213 patients with MPDs, approximately 60 (28%) patients were positive for the JAK2 (V617F) mutation. Polycythemia Vera (PV, 42.11%) was the most common MPD, followed by Essential Thrombocythemia (ET, 29.82%), Primary Myelofibrosis (MF, 12.28%), and Chronic Myeloid Leukemia (CML, 10.5%). A significant relationship between all types of MPDs and the clinical course (p< 0.05) was observed. The relationship between age and gender among all types of MPD disease was not significant (p> 0.05).
Conclusions: Of the examined cohort in North Eastern Iran, 28% of the patients with MPNs were found to have the JAK2 (V617F) mutation which determining the presence of the JAK2 (V617F) mutation helps to decide the correct form of treatment.
Methods: A total of 213 patients with myeloproliferative diseases (MPDs), were included in the study. Real-time PCR was used to detect the presence of the JAK2 (V617F) mutation in the genomic DNA isolated from patient peripheral blood samples.
Results: Of the 213 patients with MPDs, approximately 60 (28%) patients were positive for the JAK2 (V617F) mutation. Polycythemia Vera (PV, 42.11%) was the most common MPD, followed by Essential Thrombocythemia (ET, 29.82%), Primary Myelofibrosis (MF, 12.28%), and Chronic Myeloid Leukemia (CML, 10.5%). A significant relationship between all types of MPDs and the clinical course (p< 0.05) was observed. The relationship between age and gender among all types of MPD disease was not significant (p> 0.05).
Conclusions: Of the examined cohort in North Eastern Iran, 28% of the patients with MPNs were found to have the JAK2 (V617F) mutation which determining the presence of the JAK2 (V617F) mutation helps to decide the correct form of treatment.
Type of Article: Original Article |
Subject:
Biochemistry
Received: 2019/08/25 | Accepted: 2019/09/2 | Published: 2020/10/7
Received: 2019/08/25 | Accepted: 2019/09/2 | Published: 2020/10/7
References
1. Kim A, Strober B. Janus Kinase Inhibitors. Biologic and Systemic Agents in Dermatology: Springer; 2018. P. 187-98. [DOI:10.1007/978-3-319-66884-0_19]
2. Percy MJ, Zhao Q, Flores A, Harrison C, Lappin TR, Maxwell PH, et. al. A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis. Proc Natl Acad Sci U S A. 2006;103(3):654-9. [DOI:10.1073/pnas.0508423103] [PMID] [PMCID]
3. Bhagwat N, Koppikar P, Keller M, Marubayashi S, Shank K, Rampal R, et al. Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms. Blood. 2014;123(13):2075-83. [DOI:10.1182/blood-2014-01-547760] [PMID] [PMCID]
4. Ghafari H, Karimzadeh P, Chahardouli B, Alimoghdam K, Ghavamzadeh A, Dargahi H, et al. Evaluation of JAK2V617F mutation prevalence in Myeloproliferative Neoplasm by AS-RT-PCR. Journal of Payavard Salamat.2009;3(2):94-101.
5. Hubbard SR. Mechanistic insights into Regulation of JAK2 Tyrosine Kinase. Front Endocrinol (Lausanne). 2018;8:361. [DOI:10.3389/fendo.2017.00361] [PMID] [PMCID]
6. Ayatollahi H, Sadeghian MH, Keramati MR, Karimiani EG, Jafarian AH, Shirdel A, et al. JAK2 V617F Mutation in Adult T Cell Leukemia-Lymphoma. Indian J Hematol Blood Transfus. 2016;32(4):437-441. [DOI:10.1007/s12288-015-0620-4] [PMID] [PMCID]
7. Saharinen P, Takaluoma K, Silvennoinen O. Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Mol Cell Biol. 2000; 20(10):3387-3395. [DOI:10.1128/.20.10.3387-3395.2000] [PMID] [PMCID]
8. Williams JJ, Munro K, Palmer TM. Role of Ubiquitylation in Controlling Suppressor of Cytokine Signalling 3(SOCS3) Function and Expression. Cells. 2014;3(2):546-562. [DOI:10.3390/cells3020546] [PMID] [PMCID]
9. Ebid GT, Ghareeb M, Salaheldin O, Kamel MM. Prevalence of the frequency of JAK2 (V617F) mutation in different myeloproliferative disorders in Egyptian patients. Int J Clin Exp Pathol. 2015;8(9):11555-11559.
10. Bagheri M, Abdirad I, Maleki D, Eyshi A, Valizadeh N. Acquired mutation of the tyrosine kinase JAK2 V617F in the ABL-BCR-negative chronic myeloproliferative diseases in a population of west Azerbaijan province, Iran. Journal of Isfahan Medical School. 2018;35(459):1785-1791.
11. Langabeer SE. The JAK2 V617F mutation in isolated neutropenia. EXCLI J. 2018;17:1-2. [DOI:10.1016/j.hemonc.2016.08.006] [PMID]
12. Barosi G, Mesa R, Thiele J, Cervantes F, Campbell P, Verstovsek S, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemiamyelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22(2):437-8. [DOI:10.1038/sj.leu.2404914] [PMID]
13. Neet K, Hunter T. Vertebrate non-receptor protein-tyrosine kinase families. Genes Cells. 1996;1(2):147-69. [DOI:10.1046/j.1365-2443.1996.d01-234.x] [PMID]
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