Analysis Of Gene Mutations And Clinical Characteristics Of Myeloproliferative Neoplasms Based On Next-generation Sequencing

Background and Aim:Clinical diagnosis of myeloproliferative neoplasms（MPNs）is based on the bone marrow pathology combined with JAK2 V617 F,CALR and MPL mutations.In recent years,with the development of next-generation sequencing（NGS）technology and its clinical application,a large number of non-driving mutations related to prognosis and treatment have been discovered,and studies have revealed the relationship between specific non-driving mutations and clinical manifestations,disease progression and prognosis.Based on next-generation sequencing results,this study analyzed the distribution of driven mutations and non-driven mutations in MPNs in our center,and explored the relationship between the number and incidence of gene mutations and clinical features.Methods:Patients diagnosed with MPNs in our center from August 2017 to December2021 were followed up,and have completed related examinations including NGS.A total of 101 cases of MPNs that met the criteria were included,and the next-generation sequencing results and clinical characteristics of the patients were analyzed.Results:Among 101 patients who underwent NGS,a total of 271 gene mutations were detected in 57 kinds have been found.All patients had at least one mutation,97.03%（98/101 cases）carried driver gene mutations,68.32%（69/101 cases）had non-driver mutations in addition to driver mutations,and the number of non-driver mutations ranged from 1 to 7.Non-driving mutations with incidence > 5% in descending order are: ASXL1（23.76%）、TET2（16.83%）、EZH2（9.90%）、 DNMT3A（6.93%）and TP53（5.94%）.The incidence of the other non-driving mutations was less than 5%,and there were some differences in NGS results and clinical features among different subtypes of MPNs.Conclusion:1.MPNs NGS showed significant heterogeneity in the number,type and distribution of non-driving mutations.Epigenetic mutations were the most common in terms of function,and the non-driving mutations with the highest incidence included ASXL1 and TET2 mutations.The incidence of TP53 mutation in our center is higher than that reported in literature.2.The number of non-driving mutations was positively correlated with the grade of myelofibrosis and the proportion of bone marrow and peripheral blasts.The number of non-driving mutations in patients with advanced stage was significantly higher than that in patients with chronic stage.3.JAK2 V617 F variant allele frequency was positively correlated with myelofibrosis grade.