Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers.

摘要: Acute lymphoblastic leukemia (ALL) blasts undergo migration into layers of bone marrow fibroblasts (BMF) in vitro, utilizing the beta1 integrins VLA-4 and VL-5 as adhesion molecules. However, it has been unclear to whether this is a selective process mediated by specific chemoattractant molecules, or simply reflection highly motile nature early B cell precursors. We further characterized using transwell culture system, which two chambers were separated an 8 microm diameter microporous membrane, through leukemic cells could move. When BMF layer was grown on upper surface membrane there 84.1% reduction transmigration human pre-B ALL line NALM-6 lower chamber, compared control with no layer. Localization under confirmed ultrastructurally, suggesting possibility that directed chemotactic agent secreted BMF. The involvement chemokine stromal cell-derived factor-1 (SDF-1) next investigated. shown express m-RNA for SDF-1. Addition SDF-1 at 100 ng/ml chamber increased across 2.2-fold, also induced 1.4- 6.1-fold increase movement chamber. receptor SDF-1, CXCR4, demonstrated flow cytometry all 10 cases precursor-B analyzed, well NALM-6, KM-3 REH lines. An inhibitory antibody CXCR4 able block monolayers plastic 51%, nine 8-40%, partially inhibit along concentration gradient. These results confirm selectively localize within stroma due binding its cells. may be important influencing localization microenvironmental inches regulate their survival proliferation.