摘要：

The chemokine, stromal cell-derived factor-1 alpha (alpha) and its receptor (, ) are thought to be involved in the trafficking of hematopoietic progenitors and stem cells, as suggested by the chemotactic effect of alpha on these cells. Gene inactivation studies have shown that both alpha and are essential for B lymphopoiesis. Migration of leukemic cells may also be dependent on alpha and . (FN) is a component of the (), and one of the natural supports for in their bone hematopoietic environment. In the present study, we examined the influence of FN on the chemotactic effect of alpha and on the expression and function on precursor-B () cells at sequential stages of . Fourteen children with were studied. Their immunophenotypes belonged to the first three stages of . Despite relatively high levels of expression at all stages, the responsiveness to alpha, measured as the percentage of migrating cells in the transwell culture system, varied with patients and seems to be less significant for pre-B3 (and pre-B1) than for pre-B2. There was no correlation (r = 0.2) between the alpha induced migration (range: 2.5-39%) and the density of (range: 46.5-97.5%). The FN, either coated on the filter (for more than 18 hours) or in soluble form, enhanced the alpha induced migration of respectively (2 fold and 1.6 fold) without influencing expression in short term cultures. Therefore, we analyzed the expression of the FN receptors, (CD49d) and (CD49e), by direct immunofluorescence, on these leukemic cells. was strongly expressed in all stages of (range: 77-97%) while expression was more variable (range: 14-94%), but no correlation with the FN-dependent increased alpha chemotactic effect was noted. In conclusion, the migratory of pre-B leukemic cells in response to alpha partly depends upon the stage of differentiation, and partly upon unexplained patient variability. Our results suggest that several molecules from the , such as FN, may be implicated in this phenomenon.

展开