Megakaryocytic differentiation is accompanied by a reduction in cell migratory potential

Megakaryocytes (MKs) have been found in the peripheral circulation, suggest ing that they can migrate out of the bone marrow. In order to evaluate if m egakaryocytic differentiation confers a migratory phenotype, we investigate d this property in the haematopoietic cell lines MO7e and UT-7/mpl and in C D34(+) progenitor cells before and after induction of differentiation by th rombopoietin (TPO). Migration was studied using a bicompartmental culture s ystem in the presence or absence of a bone marrow endothelial cell monolaye r. Preincubation with TPO led to a significant reduction in stromal cell-de rived 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 m igratory response was seen with UT-7/mpl cells (7.4% +/- 0.4% for TPO-treat ed vs. 11.1% +/- 0.01% for controls, P < 0.05), although these cells did no t migrate in response to SDF-1. CD34(+) cells partially differentiated with TPO showed decreased migration following further TPO-induced maturation (1 3.9% +/- 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 t o 4n) fraction. These results demonstrate that megakaryocytic differentiati on is accompanied by a partial suppression of the haematopoietic cell migra tory phenotype.