Expression of the 67-kDa laminin receptor in acute myeloid leukemia cells mediates adhesion to laminin and is frequently associated with monocytic differentiation

Lodgement, proliferation, and migration of leukemic cells within bone marro w (BM) microenvironment involves adhesion of these cells to the BM extracel lular matrix molecules fibronectin and laminin. The 67-kDa laminin receptor (67LR) is a nonintegrin protein with high affinity for laminin, which play s a critical role in basement membrane invasion and metastasis of cancer ce lls. By Western blotting, we documented that 67LR was strongly expressed in myelomonocytic THP1 and histiocytic U937 cells and was weakly expressed in promyelocytic HL-60 cells. In HL-60 cells, 67LR expression almost disappea red after retinoic-induced granulocytic differentiation, whereas it strongl y increased after phorbol ester-induced monocytic differentiation. We did n ot detect 67LR expression in normal BM hematopoietic cells, in precursor-B acute lymphoblastic leukemia, in chronic lymphocytic leukemia, or in chroni c myeloid leukemia in chronic phase. By contrast, we detected enhanced 67LR expression in 40% of 53 de novo acute myeloid leukemias (AMLs), which freq uently exhibited monocytic or myelomonocytic morphology and expressed CD14 and CD11a (P < 0.05). Using a colorimetric assay, we found that the express ion pattern of this receptor corresponded to a higher adhesion to laminin; the adhesion was specific because in vitro addition to laminin-coated wells of recombinant 37-kDa laminin receptor precursor (37LRP), which is the cyt oplasmic precursor containing both laminin-binding domains of cell surface 67LR, significantly reduced laminin binding of AML cells. The expression of 67LR on AML cell surface did not correlate with other differentiation and integrin antigens such as CD7, CD13, CD33, CD34, CD11b, CD11c, CD49d, CD49e , CD45RA, and CD45R0. In contrast with 67LR behavior in solid tumors, no st atistically significant difference was found between 67LR expression and an y hematological characteristic of the disease at diagnosis, nor between 67L R expression and outcome of the disease as measured by complete remission r ate, disease-free survival, or overall survival. In conclusion, our results indicate that 67LR expression mediates specific adhesion to laminin and th at the detection of this molecule may be a valuable addition to other linea ge-associated antigens in identifying monocytic-oriented AML.