Proceedings of the International scientific and practical conference ―Science at the Frontier of Civilizations‖ (March 16-18, 2026) / Publisher website: www.naukainfo.com. – Helsinki, Finland, 2026. - 145 p.

11 RUNX1 Transcription factor <2% <2% 2%-3% 20% Negative prognostic impact in all subtypes of MPN TP53 Transcription factor <2% <2% 4%-5% 16%-50% Negative prognostic impact in all subtypes of MPN, resistance to therapy PMF has the highest frequency of non-driver mutations (ASXL1, EZH2, SRSF2, U2AF1). ET and SP are less likely to harbor these mutations, but their presence signals a risk of progression to myelofibrosis or AML. The mutations may influence patient selection for allogeneic transplants or new targeted therapies [7]. Epigenetic dysregulation is a hallmark of CMP, and mutations in genes involved in DNA methylation (e.g., TET2, DNMT3A, and IDH1/2) and chromatin modification (e.g., ASXL1 and EZH2) are common. 1 In the context of PMF, mutations in IDH1/2, ASXL1, and EZH2 are defined as high-risk mutations and are associated with a poor prognosis. Although ASXL1 and EZH2 mutations are associated with reduced response to JAK inhibitor therapy, there are currently no rationally designed approaches to directly target mutant ASXL1 or EZH2. With the exception of small molecule inhibitors of mutant IDH1/2, current therapies targeting epigenetic regulators in MPN have an indirect effect [8, 9]. Our knowledge of the biology of myeloproliferative neoplasms (MPNs) has increased dramatically over the past 20 years, and this growth in knowledge has led to advances in therapy. The knowledge gained about the mutational landscape in patients with MPNs is increasingly being used to predict outcome and select optimal therapy [6]. MPNs are a genetically heterogeneous disease in which germline and somatic mutations contribute to disease initiation and progression. NGS-based methods capture this heterogeneity, and we are only at the beginning of understanding how to