Proceedings of the International scientific and practical conference ― Cambridge Science and Education Conference‖ (February 23-25, 2026) / Publisher website: www.naukainfo.com. – Cambridge, United Kingdom, 2026. - 289 p.

72 Keywords: myeloproliferative diseases, hematopoietic stem cells, JAK2, MPL and CALR mutations, COX enzymes, prostaglandins. Philadelphia-negative myeloproliferative neoplasms (MPNs) are rare clonal neoplastic diseases of myeloid hematopoietic stem cells (HSCs). These disorders are classified into polycythemia vera (PP) with a predominance of red blood cell overproduction, essential thrombocythemia (ET) with a predominance of platelet overproduction, and primary myelofibrosis (PMF) with excessive bone marrow scarring and fibrosis. The updated WHO classification also includes prefibrotic myelofibrosis (Pre-PMF), which distinguishes a group of patients with subtle phenotypic differences from ET and a higher rate of progression to myelofibrosis (MF) [1]. The prognosis is highly variable, but in general, MF significantly limits life expectancy compared with either PP or ET. A small number of individuals progress to blast phase disease, presenting as acute myeloid leukemia, which is often refractory to conventional therapy [2]. Despite the obvious differences, similarities in bone marrow morphology, propensity for arterial and venous thrombus formation, and propensity for secondary myelofibrotic or leukemic phase transformation clinically link these disorders. These phenotypic similarities were recognized long before the discovery of activating mutations in the JAK2, MPL, and CALR genes, and the demonstration of activated signaling through the Janus Kinase (JAK)/signal transducer and activator (STAT) signaling pathway, further defined these disorders. JAK2 V617F mutations are found in approximately 95% of patients with SP, with JAK2 exon 12 mutations present in virtually all remaining SP cases. The JAK2 V617F mutation is present in approximately 50% of patients with ET and PMF, with CALR and MPL mutations in the majority of the remaining patients. Triple-negative patients account for a small percentage of ET and PMF cases [2]. With modern diagnostic approaches, it is becoming increasingly clear that the quest for a clear classification is often complicated by the spectrum of phenotypic manifestations and genetic heterogeneity. A number of coexisting somatic mutations can often be found at significant variant allele frequencies alongside JAK2, MPL, or CALR mutations