Adherence of normal and neoplastic human B cell precursors to the bone marrow microenvironment

Abstract

The early development of B lineage cells occurs in the bone marrow in close association with fibroblast-like accessory cells. The integrin VLA-4 is preferentially expressed by B cell precursors and mediates adhesion of B cell precursors to bone marrow derived fibroblasts (BM-FB), which express a VLA-4 counter/receptor, VCAM-1. The functional importance of this adhesion interaction is suggested by the inhibition by anti-VLA-4 antibody of in vitro proliferation of B cell progenitor colonies grown with a BM-FB adherent layer. In order to compare adhesion requirements of normal versus neoplastic human B cell precursors, quantitative expression of adhesion proteins by primary human B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells was studied by flow cytometry. BCP-ALL cells expressed VLA-4 and VLA-5 at similar levels as normal immature B cell precursors. However, other adhesion molecules, particularly CD44, were overexpressed by the leukemic cells relative to their normal counterparts. Similar to normal B cell precursors, adhesion of BCP-ALL cells to BM-FB was inhibited by antibodies to VLA-4 and VCAM-1. These results suggest that the ordered program of adhesion protein expression and functional activation during B cell development is at least partially intact in BCP-ALL cells, and may play a role in tissue localization and growth of the neoplastic cells. The focal pattern of spreading of adherent BCP-ALL cell lines on individual cells in the BM-FB adherent layer suggests functional heterogeneity in the bone marrow microenvironment that may be essential in regulating normal and neoplastic lymphopoiesis.