title: Analysis of changes in CD20, CD55, and CD59 expression on established rituximab-resistant B-lymphoma cell lines.
abstract: Rituximab has markedly improved treatment results for B-cell lymphoma, but there are resistance problems similar to those of other chemotherapy drugs. With regard to the acquisition of rituximab resistance, there have been several reports describing the relation between rituximab and complement regulatory factors or CD20, but many points remain unclear. To further investigate acquisition of resistance to rituximab-related complement-dependent cytotoxicity (CDC), we established rituximab-resistant B-lymphoma cell lines (RAMOS) in vitro and then analyzed expression of CD20, CD55, and CD59 on these resistant cells by flow cytometry. With repeated exposure to a low concentration of rituximab and complement, RAMOS cells gradually acquired rituximab resistance, and selection and increase of CD55(bright) and CD59(bright) cell populations due to rituximab-related CDC were observed. With repeated exposure to a high concentration of rituximab and complement, RAMOS cells promptly acquired rituximab resistance, and CD20 expression of RAMOS cells was decreased. Not only selection of CD20(dim) cells but also down-modulation of CD20 caused by rituximab-related CDC appeared to cause the decrease in CD20 expression. We believe our findings will prove to be useful for prevention of or release from rituximab resistance in cases of B-cell lymphoma.
authors.affiliation: Department of Hematology and Rheumatology, Nihon University School of Medicine, Narimasu 1-28-22-502, Tokyo, Japan. take.one@beach.ocn.ne.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takei
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Umihiko
authors.initials: U
authors.lastname: Sawada
authors.forename: Hikari
authors.initials: H
authors.lastname: Ishizuka
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism*; D018957:CD59 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003165:Complement System Proteins / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism*; D000069283:Rituximab; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018958:CD55 Antigens; D018957:CD59 Antigens; D000069283:Rituximab; D003165:Complement System Proteins