Blood: AGK defects can lead to abnormal differentiation of macronuclecells and thrombocytical reduced disease

Abnormal development of macronuclear cells and abnormal thrombocytclatose production can lead to thrombocyttosis or thrombocytis, increasing the risk of bleeding or thrombocytaAGK is a mitochondrial membrane kinase that catalyzes the formation of phospholipid acid and hemolytic phospholipid acidIt has been identified that AGK mutations are the main cause of Sengers syndrome, and it has been reported that patients with Sengers syndrome exhibit a decrease in plateletsin this study,researchers found that mice with macronucleosetomy/platelet-specific AGK defects developed thrombocytopenia and spleen enlargement, mainly caused by ineffective bone marrow platelet production and excessive myelin icy, but not associated with circulating platelet apoptosisreported that the G126E mutation weakens AGK kinase activityThe researchers found that the AGK G126E mutation did not affect peripheral platelet counts or macronuclecell differentiation, suggesting that AGK's involvement in macronucleocytes and platelet organisms' development did not depend on their kinase activityThe Mpl/JAK2/Stat3 pathway is the main signaling pathway for regulating the development of macronuclear cellsthis study confirms that AGK can bind to JAK2 in macronuclecells/plateletsIn addition, the researchers found that the JAK2 V617F mutation significantly enhanced the binding of AGK to JAK2 and significantly promoted JAK2/Stat3 signal conduction during macroplatelet stimulationThe researchers also found that the JAK2 JH2 domain peptide YGVCF617CGDENI sequence enhances the binding of AGK to JAK2, and that permeable cellular peptides containing the YGVCF617CGDENI sequence accelerate platelet formationin summary, this study reveals the crucial role of AGK in the differentiation of macronuclecells and the occurrence of platelet organisms, suggesting that the correlation between AGK and JAK2 may be a new therapeutic sequencing of thrombocytopenia or thrombocytopenia