In vitro studies of megakaryocytopoiesis in thrombocytotic disorders of man

Increased numbers of bone marrow megakaryocytes and thrombocytosis are frequently observed in patients with myeloproliferative disorders (MPD). Increased marrow megakaryocytes and thrombocytosis are also noted in a variety of inflammatory and neoplastic disease leading to the phenomenon of reactive thrombocytosis (RT). The pathogenesis of this finding remains incompletely understood. Using methodology developed in our laboratory, we investigated the causative role of megakaryocyte colony-stimulating activity (Meg-CSA) in generating this phenomenon. We also examined the cloning efficiency of colony-forming units-megakaryocyte (CFU-M) and their responsiveness to an exogenous source of Meg-CSA in patients with these diseases. The results of our investigations suggest that: (1) increased production of Meg-CSA is not responsible for the megakaryocyte hyperplasia and thrombocytosis noted in these patients; (2) the intrinsic stem cell defect described in MPD appears to affect the CFU-M of these patients as well, resulting in an effective expansion of the CFU-M pool with consequent megakaryocyte hyperplasia and thrombocytosis; (3) the CFU-M of patients with MPD remain responsive to an exogenous source of Meg-CSA, suggesting that this megakaryocyte hyperplasia may not be entirely autonomous of its effects; and (4) the CFU-M pool in RT is normal both in size and responsiveness to Meg-CSA, suggesting that in these disorders, the stimulus leading to megakaryocyte hyperplasia and thrombocytosis is active at the post-CFU-M level of megakaryocyte differentiation.