Proceedings of the International scientific and practical conference ―Science at the Frontier of Progress‖ (June 8-10, 2026) / Publisher website: www.naukainfo.com. – Paris, France, 2026. - 178 p.

23 And Repair IL-22 JAK1 TYK2 STAT3 Maintaining the integrity of the epithelial barrier Hematopoiesis EPO JAK2 STAT5 Stimulation of red blood cell production TPO JAK2 STAT5 Regulation of platelet production GM-CSF JAK2 STAT5 Stimulation of granulocyte and macrophage production G-CSF JAK2 STAT3 Stimulation of neutrophil production Growth and Metabolism GH JAK2 STAT5 Growth and metabolism stimulation Leptin JAK2 STAT3 Appetite and metabolism control Today, the cause of chronic myeloproliferative neoplasms (CMPN) can be established in most cases at the molecular genetic level. According to the WHO classification of 2022, the group of Ph-negative CMPN includes: polycythemia vera (PT), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Usually, acquired somatic mutations are found in the Janus Kinase 2 (JAK2), Thrombopoietin Receptor (MPL) and Calreticulin (CALR) genes (up to 90% of cases), which lead to permanent activation of the JAK/STAT intracellular signaling pathway and the establishment of a myeloproliferative phenotype [7, 8, 9]. The canonical JAK/STAT signaling pathway is initiated when a cytokine or hormone binds to its specific transmembrane receptor expressed on the surface of a target cell. This interaction induces receptor dimerization or conformational reorganization, facilitating the assembly and activation of receptor-associated Janus kinases (JAKs). The four members of the JAK family—JAK1, JAK2, JAK3, and TYK2—are activated by transphosphorylation and subsequently phosphorylate specific tyrosine residues within the cytoplasmic domains of the receptor. These phosphotyrosine motifs serve as docking sites for cytoplasmic STAT family proteins, particularly STAT1–STAT6, which are recruited via their SH2 domains. Disruption of normal JAK/STAT protein function, particularly through mutations, has been associated with a wide range of human diseases, particularly innate immune defects and hematological malignancies. The JAK/STAT signaling pathway, consisting of JAK kinase and signal transducer and activator of transcription (STAT) protein, transmits information from extracellular polypeptide signals, via transmembrane receptors, directly to the promoters of target genes in the nucleus [9, 10, 11]. STAT family proteins mainly act as transcription factors. STAT proteins contain several functional domains. The SH2 domain is formed by two α-helices and a β-sheet and contains approximately 575–680 amino acid residues. At the C-terminus are located transcriptional activation domains TAD [8, 9, 12]. JAK2 kinase is a member of the non-receptor tyrosine kinase family and is one of four JAK kinases. The JAK1, JAK2, and TYK2 genes are found in all mammalian cells, while JAK3 is found only in hematopoietic cells. They are essential for the growth, survival, proliferation and differentiation of a variety of cells, and are also important for hematopoietic cells. The JAK2 gene is located on chromosome 9 (9p24) in humans, includes 25 exons, and the protein synthesized by this gene contains 1132 amino acid residues with a total mass of 120–140 kDa. Structurally, it consists of seven homologous regions (JH1–7), which form four domains: kinase (JH1), pseudokinase (JH2), domain with homology to the Sarc oncoprotein (SH2; JH3–4), FERM-homology domain (JH4–7; F – protein 4.1, E – ezrin, R – radixin, M – moesin) [13]. JAK kinases at the cellular level are located in the cytoplasm and localized near endosomes and the cell membrane. They are normally inactive and associated with the cytoplasmic end of cytokine receptors types 1 and 2, such as the erythropoietin receptor (EPO-R), the thrombopoietin receptor (TPO-R), the granulocyte colony-stimulating factor receptor (G-CSFR), the interferon-gamma (INF-γ) receptor for interleukins (IL), and many others. After the receptor interacts with the appropriate ligand, a key JAK domain is phosphorylated, which undergoes conformational changes and becomes activated. In turn, JAK phosphorylation mediates phosphorylation of tyrosine residues in the cytoplasmic domains of receptors and thus creates a site that activates a number of proteins, ultimately leading to activation of the signal transducer and activator of transcription (STAT), mitogen-activated protein (MAP) and phosphatidylinositol 3-kinase- AKT (PI3K-AKT) pathways. Activated STAT dimerizes and translocates to the nucleus, where it regulates transcription after binding to specific consensus sequences in the promoter regions of certain target genes. The entire process is tightly controlled at multiple levels by protein tyrosine phosphatases (PTPs),