Megakaryocytic differentiation is accompanied by a reduction in cell migratory potential

Megakaryocytes (MKs) have been found in the peripheral circulation, suggesting that they can migrate out of the bone marrow. In order to evaluate if megakaryocytic differentiation confers a migratory phenotype, we investigated this property in the haematopoietic cell lines MO7e and UT-7/mpl and in CD34(+) progenitor cells before and after induction of differentiation by thrombopoietin (TPO). Migration was studied using a bicompartmental culture system in the presence or absence of a bone marrow endothelial cell monolayer. Preincubation with TPO led to a significant reduction in stromal cell-derived factor-1 (SDF-1)-induced migration of MO7e cells (0.7% +/- 0.08% for TPO-treated vs. 2.6% +/- 0.3% for controls P < 0.05). A similar decreased migratory response was seen with UT-7/mpl cells (7.4% +/- 0.4% for TPO-treated vs. 11.1% +/- 0.01% for controls, P < 0.05), although these cells did not migrate in response to SDF-1. CD34(+) cells partially differentiated with TPO showed decreased migration following further TPO-induced maturation (13.9% +/- 1.8% for TPO-treated vs. 24.1% +/- 1.8% for untreated, P < 0.05). This reduction was more pronounced in the large MK (greater than or equal to 4n) fraction. These results demonstrate that megakaryocytic differentiation is accompanied by a partial suppression of the haematopoietic cell migratory phenotype.