BETA-1-INTEGRINS DOMINATE CELL TRAFFIC OF LEUKEMIC-CELLS IN HUMAN BONE-MARROW STROMA

Migration patterns of leukemic cells in bone marrow are largely regula ted by cell contacts between leukemic cells and stromal cells or extra -cellular matrix. The mechanism of this interaction with bone-marrow s tromal cells was studied in a human in vitro model. Migration behavior of erythroleukemia cell line K562, derived from a patient with chroni c myeloid leukemia, was compared with that of the erythroleukemia cell line HEL92.1.7 and the promyelocytic leukemia cell line HL60 from acu te leukemias. Interaction varied between low binding affinity (K562) t o intensive cell interaction (HEL92.1.7) followed by invasion into the stromal cell monolayer. Some of the HL60 cells adhered to stromal cel ls, while the remainder migrated into the stromal cell monolayer. The role of adhesion molecules in these cell interactions was determined. Distinct expression of beta(1)-integrins ICAM-1, CD44 and VCAM-1 was d etected on the different cell lines. Inhibition studies pointed to a d ominant role of VLA-4- and VLA-5-mediated interactions. K562 lacked VL A-4 and a low affinity of the VLA-5 on these cells resulted in an abse nce of binding to the bone-marrow stroma. These results indicate the V LA-5/fibronectin, VLA-4/fibronectin and the VLA-4/VCAM-1 interaction p athways between leukemic cells and bone-marrow stroma. (C) 1996 Wiley- Liss, Inc.