MPL receptor dimerization and the thrombopoietin pathway in primary immune thrombocytopenia: from molecular mechanisms to targeted therapies

Primary immune thrombocytopenia (ITP) is characterized by the dual pathology of peripheral immune-mediated platelet clearance and restricted platelet production by megakaryocytes. The TPO-MPL axis is a central regulator of platelet homeostasis, and ligand-induced receptor activation is associated with downstream JAK2-STAT, MAPK, and PI3K-AKT signaling. This review summarizes the structural and functional features of TPO and MPL, the major immunopathogenic mechanisms of ITP, and the current clini