New insights for GPIb-IX-V/vWF axis-dependent inherited macrothrombocytopenias – macRoIT

Molecular defects in any step megakaryopoiesis, a process that achieves the platelet production, can lead to thrombocytopenia that could be inherited or acquired. Inherited macrothrombocytopenia (macroIT) represent one of three main groups of ITs and are mainly characterized by mutations in genes involved in cytoskeleton reorganization. Here, we will focus on mechanisms leading to three macroIT involving GPIb/GPIX/GPV-vWF axis: Bernard Soulier Syndrome with mutations in GP1BB, GP1BA and GP9 leading to a decrease or absence of GPIb/GPIX/GPV complex at the cell surface on one hand, and von Willebrand disease type 2B and Platelet type-von Willebrand disease with gain-of–function mutations in VWF and GP1BA respectively on the other hand. The main objective will be to understand the role of the GPIB complex-vWF axis as a central signaling integrator during MKpoiesis to understand how different type of mutations in the same genes lead to the similar phenotype and to improve the stratification of patients by targeting the deregulated signaling pathways.