lewis-x-antigen and Leukemic-Infiltration

Leukostasis and tissue infiltration by leukemic cells are poorly understood life-threatening complications of acute leukemia. This study has tested the hypothesis that adhesion receptors and cytokines secreted by blast cells play central roles in these reactions. Immunophenotypic studies showed that acute myeloid leukemia (AML) cells (n = 78) of the M0 to M5 subtypes of the French-American-British Cooperative Group expressed various amounts of adhesion receptors, including CD11a, b, c/CD18, CD49d, e, f/CD29, CD54, sCD15, and L-selectin. The presence of functional adhesion receptors was evaluated using a nonstatic adhesion assay. The number of blast cells attached to unactivated endothelium increased by 7 to 31 times after a 6-hour exposure of endothelium to tumor necrosis factor (TNF)-alpha. Inhibition studies showed that multiple adhesion receptors--including L-selectin, E-selectin, VCAM-1, and CD11/CD18--were involved in blast cell adhesion to TNF-alpha-activated endothelium. Leukemic cells were then cocultured at 37 degrees C on unactivated endothelial cell monolayers for time periods up to 24 hours. A time-dependent increase in the number of blasts attached to the endothelium and a concomitant induction of ICAM-1, VCAM-1, and E-selectin were observed. Additional experiments revealed that endothelial cell activation by leukemic myeloblasts was caused by cytokine secretion by blast cells, in particular TNF-alpha and IL-1 beta, and direct contacts between adhesion receptors expressed by blast cells and endothelial cells. Thus, leukemic cells have the ability to generate conditions that promote their own adhesion to vascular endothelium, a property that may have important implications for the pathophysiology of leukostasis and tissue infiltration by leukemic blast cells. (Blood. 2001;97:2121-2129)

Topics: Antigens, CD; CD18 Antigens; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Coculture Techniques; E-Selectin; Endothelium, Vascular; Gene Expression Regulation, Leukemic; Humans; Integrin alpha4; Integrin alpha5; Integrin alpha6; Integrin alphaXbeta2; Integrin beta1; Intercellular Adhesion Molecule-1; Interleukin-1; L-Selectin; Leukemia, Myeloid; Leukemic Infiltration; Leukostasis; Lewis X Antigen; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Neoplasm Proteins; Neoplastic Stem Cells; Receptors, Lymphocyte Homing; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

We describe the clinicopathological features of eight cases of Ki-1 positive anaplastic large cell malignant lymphoma (Ki-1 ALCL) in which there was extensive infiltration by eosinophils and/or neutrophils in the absence of necrosis.. The patients comprised four males and four females with an age range of 24-74 years. Five cases had originally been diagnosed as Hodgkin's disease and one as true histiocytic lymphoma. In all cases, there was massive infiltration by eosinophils and/or neutrophils sometimes to such an extent that malignant cells were obscured. Immunohistochemical staining was performed using the monoclonal antibodies CD30, CD15, CD45, CD20, CD3, CD45RO, epithelial membrane antigen (EMA), CAM5.2, vimentin and CD68. In all cases, tumour cells were strongly positive for CD30 but negative for CD15. One case was positive for CD45 but none expressed B or T-cell markers. Five cases were positive for vimentin and two for EMA. Three of seven patients in whom adequate clinical details were available had stage III or IV disease at presentation and four exhibited B symptoms. Four patients had a peripheral neutrophilia and one a peripheral eosinophilia.. The study shows that an eosinophil and/or neutrophil-rich variant of Ki-1 ALCD exists, expanding the morphological spectrum of this tumour.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Eosinophils; Female; Humans; Immunohistochemistry; Ki-1 Antigen; Leukemic Infiltration; Lewis X Antigen; Lymph Nodes; Lymphoma, Large-Cell, Anaplastic; Male; Middle Aged; Neutrophils

A subset of human helper memory T cells is known to adhere to E-selectin expressed on cytokine-activated endothelial cells. However, sialyl Lex antigen, the carbohydrate ligand for E-selectin, has been hardly detectable on these cells, at least when typical anti-sialyl Lex antibodies were used for detection. One of the MoAbs (2F3, IgM), which we raised against a chemically synthesized sialyl Lex glycolipid preparation, is found to react selectively to CD4+ CD45RObright+ CD45RA- helper memory T cells among peripheral lymphocytes in healthy individuals. The specificity of the antibody is in clear contrast to that of the hitherto reported typical anti-sialyl Lex antibodies FH-6 and SNH-3. These classical anti-sialyl Lex antibodies were known to react to a subset of natural killer (NK) cells, but were not reactive with any particular subset of resting peripheral T or B cells of healthy individuals if the cells were not activated. On the other hand, the newly generated 2F3 antibody specifically reacted to helper memory T cells, and did not react to NK cells, B cells, or any T cells other than helper memory T cells. When tested against the sialyl Lex-active glycolipid antigen, the reactivity of 2F3 was not significantly different from that of the classical anti-sialyl Lex antibodies. But when tested against oligosaccharides prepared from cellular glycoproteins, 2F3 detected a distinct set of O-linked oligosaccharides, which were not reactive to the classical anti-sialyl Lex antibodies. Our results suggest that various molecular species of sialyl Lex antigens are present on carbohydrate side chains of cellular glycoproteins, and that helper memory T cells express a distinct type of sialyl Lex antigen that is defined by 2F3 but is not efficiently detected by other typical anti-sialyl Lex antibodies. Among cultured lymphocytic leukemia cells, the adult T-cell leukemia (ATL) cells preferentially expressed the 2F3-defined antigen, and acute lymphocytic leukemia cells rarely expressed the antigen. The cultured ATL cells expressing the 2F3-defined antigen showed a clear E-selectin-dependent adhesion to cytokin-activated endothelial cells, and the 2F3-defined sialyl Lex antigen served as a ligand for E-selectin as ascertained by the clear inhibition of adhesion with the 2F3 antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Antibodies, Monoclonal; Cell Adhesion Molecules; Cells, Cultured; E-Selectin; Humans; Immunologic Memory; Leukemia, T-Cell; Leukemic Infiltration; Leukocyte Common Antigens; Lewis X Antigen; Skin; T-Lymphocytes, Helper-Inducer