Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells.
Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions.
Evans
S S
SS
Department of Molecular Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Lee
D B
DB
Han
T
T
Tomasi
T B
TB
Evans
R L
RL
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology*; D000943:Antigens, Differentiation / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002449:Cell Aggregation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D007943:Leukemia, Hairy Cell / Q000378:metabolism / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology; D015463:Leukemia, Prolymphocytic / Q000378:metabolism / Q000473:pathology; D009705:Nucleosides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007370:Interferon Type I; D009705:Nucleosides; C062010:leu-13 antigen; D015847:Interleukin-4; D003513:Cycloheximide