PB2178: EVALUATION OF JAK2 EXON 12 MUTATIONS IN PATIENTS WITH JAK2 (V617F)-NEGATIVE POLYCYTHEMIA VERA

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Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: Polycythemia vera (PV) disease is an acquired and clonal stem cell disorder characterized by abnormal erythropoiesis. Identifying a unique mutation of increased activity in the Janus kinase 2 (JAK2) gene in patients with chronic myeloproliferative disorders has provided a beneficial diagnostic method. Aims: The present study evaluated exon 12 mutations in the JAK2 gene in patients with PV who had no V617F mutation. Methods: This cross-sectional study was conducted on adult patients with PV who were referred to the blood department of Shariati Hospital (Tehran, Iran) between 2013 and 2016. All samples were sent for flow cytometry to check cells for leukemia and cell line. Further, chromosomal karyotype was checked by the metaphase culture method on all samples. In this study, cDNA was isolated from the samples of PV patients without the V617F mutation. Sequencing was performed using the BigDye Terminator Sequencing Kit (Applied Biosystems), version 1.1. The identified sequence was then confirmed by Sanger sequencing. Finally, the presence of the mutation in the determined sequence was examined by DNASIS software. Ultimately, the data were statistically analyzed using SPSS software, version 22. Results: In general, 150 patients with an average age of 46.30±19.50 years were included in this study. In 12 patients (eight percent), mutations were detected in the exon 12 of the JAK2 gene, including two novel genetic mutations (NG_009904.1:g.89793T>G and NG_009904.1 (JAK2_i001)) that had not been reported previously (Figure1). A significant decrease was observed in the platelet count, while a significant increase was found in the hemoglobin level in patients with mutations compared to patients without mutations (P<0.001, P=0.023). Among 23 patients, the average percentage of the bone blast was 1.78±0.95, and out of 25 patients, three cases had mutations in exon 12, and all of them had increased erythropoiesis.Figure 1. Electropherogram of a patient with a newly identified mutation in the JAK2 gene exon 12. The top and bottom pictures show the sample without and with mutations, respectively. The result of sequencing in this patient was the substitution of G nucleotide acid instead of T nucleotide at position 89793, resulting in the substitution of amino acid lysine instead of asparagine at position 542 (Asn542Lys). Summary/Conclusion: Overall, a relationship was found between hemoglobin and platelet levels with mutations in exon 12. In terms of polymorphism, heterozygote was the most common type, and the JAK2 gene mutation in exon 12 was observed in all patients with erythrocytosis. These findings can help better diagnose and find better treatment methods for PV patients in future studies. Keywords: Gene mutation, Mutation, Kinase domain mutant, Polycythemia vera

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