The effects of low-dose vincristine on megakaryocyte colony-forming cells and megakaryocyte ploidy.

The administration of low-dose vincristine (VCR) (0.1 mg/kg) to mice resulted in thrombocytosis without prior thrombocytopenia. No significant changes in marrow megakaryocyte numbers were found. However, after a minor early decrease, mean megakaryocyte ploidy increased, with a peak at 3 d. The number of megakaryocyte colony-forming cells (MEG-CFC) in bone marrow did not change significantly. In contrast with the effects on marrow, the concentration of megakaryocytes and the content of MEG-CFC in the spleen were significantly reduced for 1-2 d after VCR. This reduction was followed by a compensatory rise in the splenic content of MEG-CFC (peak 3-fold increase at 3 d), and 1-2 d later, an increase in splenic megakaryocytes which was concurrent with the increased platelet count. Culture of marrow and spleen cells in the presence of VCR resulted in inhibition of megakaryocyte colony formation at concentrations greater than 5 ng/ml and parallel reduction of the number of megakaryocytes per colony and the mean ploidy of colony megakaryocytes. The results suggest that the thrombocytosis induced by low-dose VCR does not result simply from an effect on platelets, but reflects compensatory changes in megakaryopoiesis secondary to toxic suppression of megakaryocytes and their progenitors.