Frequency of JAK2 and MPL Mutation in BCR/ABL Negative Myelofibrosis in KPK
Introduction: BCR-ABL1-negative myeloproliferative disorders are a sub-group of myeloproliferative neoplasms (MPNs) that consist of polycythemia Vera (PV), Essential thrombocythemia (ET) and Primary Myelofibrosis (PMF). Over the past decade, the morphological and clinical division of myeloproliferative neoplasms (MPN) has changed to a classification that describes the molecular heterogeneity and is unique to this subgroup of haematological malignancies. This includes alterations in Janus kinase 2 (JAK2), and MPL genes.
Objective: To determine the frequency of JAK2 (p.V617F) and MPL (p.W515L) mutation in primary myelofibrosis in KPK province of Pakistan.
Materials and Methods: Fifty patients with PMF were enrolled in the study. JAK2 mutation status was determined using allele specific primers and MPL mutation was detected by direct Sanger sequencing technique. The data was analyzed using BioEdit by aligning the sequence data with reference genome hg19 assembly.
Results: Among 50 patients, 41 patients were diagnosed with PMF, while 9 patients had secondary myelofibrosis i.e. Post PV-MF and Post ET-MF. Out of the 41 PMF patient 2 patients had MPL gene variation, while one of the Post ET –MF had a MPL gene variation. Forty eight (96%) were positive for JAK2 mutation. Five patients who had MPL mutation also showed JAK 2 mutation. Two of the MPL positive patients were also positive for JAK2 mutation.
Conclusion: We reported rate of recurrence of JAK2 mutation in 96% of the cases and MPL exon 10 mutations in 6% of the cases.
2. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Vol. 114, Blood. Blood; 2009. p. 937–51.
3. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Vol. 127, Blood. Blood; 2016. p. 2391–405.
4. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in Understanding and Management of Myeloproliferative Neoplasms. CA Cancer J Clin. 2009 May 1;59(3):171–91.
5. A T. The history of myeloproliferative disorders: before and after Dameshek. Leukemia. 2008;22(1):3–13.
6. James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144–8.
7. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar;365(9464):1054–61.
8. Xia J, Lu MZ, Jiang YQ, Yang GH, Zhuang Y, Sun HL, et al. JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in Chinese patients with primary myelofibrosis. Chinese J Cancer Res. 2012 Mar;24(1):72–6.
9. Vakil E, Tefferi A. BCR-ABL1-negative myeloproliferative neoplasms: A review of molecular biology, diagnosis, and treatment. In: Clinical Lymphoma, Myeloma and Leukemia. Clin Lymphoma Myeloma Leuk; 2011.
10. Ghotaslou A, Nadali F, Chahardouli B, Alizad Ghandforosh N, Rostami SH, Alimoghaddam K, et al. Low frequency of c-MPL gene mutations in Iranian patients with Philadelphia-negative myeloproliferative disorders. Iran J Pediatr Hematol Oncol. 2015;5(1):43–439.
11. Eldeweny S, Ibrahim H, Elsayed G, Samra M. MPL W515 L/K mutations in myeloproliferative neoplasms. Egypt J Med Hum Genet. 2019 Dec 12;20(1):1–7.
12. Lin Y, Liu E, Sun Q, Ma J, Li Q, Cao Z, et al. The prevalence of JAK2, MPL, and CALR mutations in Chinese patients with BCR-ABL1-Negative Myeloproliferative Neoplasms. In: American Journal of Clinical Pathology. Am J Clin Pathol; 2015. p. 165–71.
13. Xu W, Li JY, Xia J, Zhang SJ, Fan L, Qiao C. MPL W515L mutation in Chinese patients with myeloproliferative diseases. Leuk Lymphoma. 2008 May;49(5):955–8.
14. Usseglio F, Beaufils N, Calleja A, Raynaud S, Gabert J. Detection of CALR and MPL Mutations in Low Allelic Burden JAK2 V617F Essential Thrombocythemia. J Mol Diagnostics. 2017 Jan 1;19(1):92–8.
15. Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martínez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014 Aug 14;124(7):1062–9.
16. Akpinar TS, Hançer VS, Nalçaci M, Diz-Küçükkaya R. Kronik miyeloproliferatif neoplazmlarda MPL W515L/K mutasyonlari. Turkish J Hematol. 2013;30(1):8–12.
17. Hamayun S, Farooq G, Marwat MA, Batool Z, Ali N, Gul S, et al. Frequency of JAK2 mutation in BCR-ABL negative myeloproliferative neoplasms in khyber. 2017;403–6.
18. Latif S, Khan SA, Mahmood A, Mahmood R. Frequency of MPL and JAK2 exon 12 gene mutation in myeloproliferative neoplasms. 2020;70(3):746–50.
Copyright (c) 2022 Ayesha Gul, Sheeba Ishtiaq, Hina Umair, Memoona Rasheed
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
All research articles published in the Journal of Rawalpindi Medical College (JRMC) are fully open access: immediately freely available to read, download, and share. Copyrights of all articles published in JRMC are retained by the authors. First publication rights are granted to JRMC. The journal/publisher is not responsible for subsequent uses of the work.
All articles are published under the Creative Commons Attribution (CC BY-SA 4.0) license.