Prevalence of JAK2V617F, CALR in Philadelphia Positive and Negative Myeloproliferative Neoplasm

  • Elham Abedi 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mehran Karimi 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Nader Cohan 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Sezaneh Haghpanah 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Ramin Yaghobi 2- Transplant research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Negar Azarpira 2- Transplant research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mohamad Moghadam 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Elahe Bayat 3- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Farnoush Farokhian 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Hamid Mohammadi 4- Pediatric department, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  • Elahe Razmara lak 5- Department of Medical laboratory sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences
  • Habib allah Golafshan 6- Department of Medical laboratory sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mani Ramzi 1- Hematology research center, Shiraz University of Medical Sciences, Shiraz, Iran
Keywords: Myeloproliferative Neoplasms, Genetic Abnormality, CALR, JAK2, Philadelphia Chromosome

Abstract

Background: Myeloproliferative neoplasms (MPNs) are heterogeneous disorders with a variety of genetic abnormalities. We aim to assess the prevalence of Calreticulin (CALR) and JAK2 mutations in Iranian MPNs. Materials and Methods: In a cross-sectional study, CALR and JAK2 mutations among 130 MPNs patients, including 78 Philadelphia chromosome-negative (MPN-) and 52 Philadelphia chromosome-positive (MPN+) as well as 51 healthy control subjects, were investigated by GAP-PCR. Results: In MPN- group JAK2 and CALR gene mutations were found in 64.1% and 7.7%, respectively, that 5.1% were positive for both mutations, and 2.6% had only CALR mutation. In polycythemia vera (PV) patients 90% had JAK2 mutation, which was significantly higher than other MPN- or MPN+ patients. Most of the MPN+ patients had neither mutation in CALR nor JAK2 (70% CALR-/JAK2-). Among all patients’ groups, the prevalence of CALR+ mutation in either rs1450785140 (4 cases) or rs765476509 (5 cases) position was not statistically different. Conclusion: These results showed a low prevalence of CALR mutations in all types of MPNs in the Iranian population that its frequency may influence by ethnicity and genetic diversity. CALR mutation may be seen in JAK2 negative cases, also. The PV had the highest JAK2 mutation with a 90 percent positivity rate among MPNs cases. [GMJ.2021;10:e2127]

References

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. Blood. 2016;127(20):2391-405.

https://doi.org/10.1182/blood-2016-03-643544

PMid:27069254

Wong WJ, Pozdnyakova O. Myeloproliferative neoplasms: Diagnostic workup of the cythemic patient.Int J Lab Hematol. 2019;41 suppl:142-50.

https://doi.org/10.1111/ijlh.13005

PMid:31069979

Zhou T, Medeiros LJ, Hu S. Chronic Myeloid Leukemia: Beyond BCR-ABL1. Curr Hematol Malig Rep. 2018;13(6):435-45.

https://doi.org/10.1007/s11899-018-0474-6

PMid:30370478

O'Sullivan J, Mead AJ. Heterogeneity in myeloproliferative neoplasms: Causes and consequences. Adv Biol Regul. 2019;71:55-68.

https://doi.org/10.1016/j.jbior.2018.11.007

PMid:30528537

James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-8.

https://doi.org/10.1038/nature03546

PMid:15793561

Gango A, Mozes R, Boha Z, Kajtar B, Timar B, Kiraly PA, et al. Quantitative assessment of JAK2 V617F and CALR mutations in Philadelphia negative myeloproliferative neoplasms. Leuk Res. 2018;65:42-8.

https://doi.org/10.1016/j.leukres.2017.12.005

PMid:29306106

Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-90.

https://doi.org/10.1056/NEJMoa1311347

PMid:24325356

Cazzola M, Kralovics R. From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms. Blood. 2014;123(24):3714-9.

https://doi.org/10.1182/blood-2014-03-530865

PMid:24786775

Langabeer SE, Andrikovics H, Asp J, Bellosillo B, Carillo S, Haslam K et al. Molecular diagnostics of myeloproliferative neoplasms. Eur J Haematol. 2015;95(4):270-9.

https://doi.org/10.1111/ejh.12578

PMid:25951317

Nangalia J, Green TR. The evolving genomic landscape of myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program. 2014;2014(1):287-96.

https://doi.org/10.1182/asheducation-2014.1.287

PMid:25696868

Bilbao-Sieyro C, Florido Y, Gómez-Casares MT. CALR mutation characterization in myeloproliferative neoplasms. Oncotarget. 2016;7(33):52614-7.

https://doi.org/10.18632/oncotarget.10376

PMid:27384487 PMCid:PMC5288135

Giannopoulos A, Rougkala N, Loupis T, Mantzourani M, Viniou N-A, Variami E et al. Detection of CALR Mutations Using High Resolution Melting Curve Analysis (HRM-A); Application on a Large Cohort of Greek ET and MF Patients. Mediterr J Hematol Infect Dis. 2019;11(1):e2019009.

https://doi.org/10.4084/mjhid.2019.009

PMid:30671215 PMCid:PMC6328041

Wong WJ, Hasserjian RP, Pinkus GS, Breyfogle LJ, Mullally A, Pozdnyakova O. JAK2, CALR, MPL and ASXL1 mutational status correlates with distinct histological features in Philadelphia chromosome-negative myeloproliferative neoplasms. Haematologica. 2018;103(2):e63-e8.

https://doi.org/10.3324/haematol.2017.178988

PMid:29146710 PMCid:PMC5792288

Imai M, Araki M, Komatsu N. Somatic mutations of calreticulin in myeloproliferative neoplasms. Int J Hematol. 2017;105(6):743-7.

https://doi.org/10.1007/s12185-017-2246-9

PMid:28470469

Chao MP, Jaiswal S, Weissman-Tsukamoto R, Alizadeh AA, Gentles AJ, Volkmer J et al. Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med. 2010;2(63):63-94.

https://doi.org/10.1126/scitranslmed.3001375

PMid:21178137 PMCid:PMC4126904

Poopak B, Hagh MF, Saki N, Elahi F, Rezvani H, Khosravipour G et al. JAK2 V617F mutation in Iranian patients with myeloproliferative neoplasms: clinical and laboratory findings. Turkish Journal of Medical Sciences. 2013;43(3):347-53.

https://doi.org/10.3906/sag-1205-11

Hamid M, Shahbazi Z. Prevalence of JAK2 V617F Mutation in Iranian Patients with Myeloproliferative Neoplasms. Arch Med Lab Sci. 2020;6:1-7 (e5).

Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-7.

https://doi.org/10.1038/leu.2014.3

PMid:24402162

Nunes DP, Lima LT, Chauffaille Mde L, Mitne-Neto M, Santos MT, Cliquet MG et al. CALR mutations screening in wild type JAK2(V617F) and MPL(W515K/L) Brazilian myeloproliferative neoplasm patients. Blood Cells Mol Dis. 2015;55(3):236-40.

https://doi.org/10.1016/j.bcmd.2015.07.005

PMid:26227853

Ojeda MJ, Bragos IM, Calvo KL, Williams GM, Carbonell MM, Pratti AF. CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms. Hematology. 2018;23(4):208-11.

https://doi.org/10.1080/10245332.2017.1385891

PMid:28990497

Haslam K, Conneally E, Flynn CM, Cahill MR, Gilligan O, O'Shea D et al. CALR mutation profile in Irish patients with myeloproliferative neoplasms. Hematol Oncol Stem Cell Ther. 2016;9(3):112-5.

https://doi.org/10.1016/j.hemonc.2016.05.002

PMid:27352261

Dogliotti I, Fava C, Serra A, Gottardi E, Daraio F, Carnuccio F et al. CALR-positive myeloproliferative disorder in a patient with Ph-positive chronic myeloid leukemia in durable treatment-free remission: a case report. Stem Cell Investig. 2017;4:57.

https://doi.org/10.21037/sci.2017.06.02

PMid:28725653 PMCid:PMC5503914

Lewandowski K, Gniot M. Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Int J Lab Hematol. 2018;40(3):366-71.

https://doi.org/10.1111/ijlh.12798

PMid:29508552

Haunstrup LM, Ebbesen LH, Hansen M, Severinsen MT, Aggerholm A. Skewed ratio between type 1 and type 2 calreticulin mutations in essential thrombocytosis patients with concomitant Janus kinase 2 V617F mutation. Exp Hematol. 2018;68:62-5.

https://doi.org/10.1016/j.exphem.2018.09.007

PMid:30292681

Zaen-Al-Abideen Pahore TS, Shamsi MT, Tasneem Farzana SH, Nadeem M, Ahmad M, Naz A. JAK2V617F mutation in chronic myeloid leukemia predicts early disease progression. J Coll Physicians Surg Pak. 2011;21(8):472-5.

Tabassum N, Saboor M, Ghani R, Moinuddin M. Frequency of JAK2 V617F mutation in patients with Philadelphia positive Chronic Myeloid Leukemia in Pakistan. Pak J Med Sci. 2014;30(1):185-8.

Published
2021-12-07
How to Cite
Abedi, E., Karimi, M., Cohan, N., Haghpanah, S., Yaghobi, R., Azarpira, N., Moghadam, M., Bayat, E., Farokhian, F., Mohammadi, H., Razmara lak, E., Golafshan, H. allah, & Ramzi, M. (2021). Prevalence of JAK2V617F, CALR in Philadelphia Positive and Negative Myeloproliferative Neoplasm. Galen Medical Journal, 10, e2127. https://doi.org/10.31661/gmj.v10i0.2127