Megakaryopoiesis and pathology
Taking advantage of our novel protocol to derive Mks from peripheral blood, we have recently identified a series of quality and quantitative defects in patient affected by ether inherited thrombocytopenias or myeloproliferative disorders (MPNs). In particular, we described a defect of proplatelet formation involving tubulin distribution that affects Mks from patients with heterozygous Bolzano mutation, and suggested that this abnormality contributes to their macrothrombocytopenia. Moreover, we studied for the first time the in vitro PPF by Mks carrying the MYH9-RD mutations, which were obtained by culture of patients’ blood progenitor cells. We demonstrated that two different MYH9 mutations cause a myosin-IIA loss-of-function, which results both in a defective regulation of PPF and in a reduced complexity of proplatelet architecture. We propose that these alterations contribute to thrombocytopenia of MYH9-RD. Finally, for the first time, we have recently demonstrated that platelet production in MPNs is strictly related to the intrinsic capacity of Mks to extend functional proplatelets and release PLTs.