ANTIBODIES TO CD44 ENHANCE ADHESION OF NORMAL CD34(-LEUKEMIA CELLS TOBONE-MARROW STROMA() CELLS AND ACUTE MYELOBLASTIC BUT NOT LYMPHOBLASTIC)

The role of CD44 in the adhesion of haemopoietic cells to bone marrow stromal layers has not been clearly defined in humans, although its im portance in the murine system has been well documented We have demonst rated that the CD44 antibody, NIH44-1, enhances the adhesion of haemop oietic cells to bone marrow stroma, Normal human CD34(+) haemopoietic progenitors and blasts from patients with acute myeloblastic, but not lymphoblastic, leukaemia responded to NIH44-1. All CD44 antibodies tes ted which bound the same epitope as NM44-1 also augmented haemopoietic fell adhesion to bone marrow adherent layers: however, antibodies whi ch bound to other CD44 epitopes showed mixed responses. Augmented adhe sion was independent of cell metabolism, suggesting that antibody bind ing resulted in direct activation of the CD44 molecule, However, hyalu ronic acid was not the ligand for induced adhesion, nor could we show a role for other CD44 ligands including fibronectin, laminin, collagen or chondroitin sulphate proteoglycan. Similarly none of the 22 CD44 a ntibodies tested inhibited the stimulatory effect of the NIH44-1. Expr ession of CD44 was not sufficient to determine NM44-1 responsiveness s ince cell lines and leukaemic tells which failed to respond to NIH44-1 expressed high levels of CD44. Neither CD44 isoforms nor glycosylatio n patterns could be identified as predictive of response. CD44 antibod ies enhanced binding of normal and leukaemic haemopoietic progenitors to bone marrow fibroblasts via an unidentified stromal ligand.