title: Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance.
abstract: CD20 is a 33- to 36-kDa transmembrane phosphoprotein involved in the activation, proliferation, and differentiation of B lymphocytes. The predicted amino acid sequence of the CD20 suggests 4 transmembrane-spanning regions with both N- and C-termini located in the cytoplasm. We demonstrate herein that significant levels of circulating CD20 (cCD20) can be detected in the plasma of patients with chronic lymphocytic leukemia (CLL) and that cCD20 interferes with the binding of rituximab, a humanized anti-CD20 monoclonal antibody, to CLL cells. An enzyme-linked immunosorbent assay (ELISA) was developed to measure circulating cCD20 levels in the plasma. We measured cCD20 levels in the plasma of 180 patients with CLL and correlated these levels with clinical characteristics and outcome. Circulating CD20 levels correlated positively with beta(2)-microglobulin level (p =.006) and percentage of CD38(+) cells (p =.03) and negatively with platelet count (p =.004) and hemoglobin level (p =.02). Patients with advanced Rai (III/IV) or Binet (C) stage disease had significantly higher levels of cCD20 than did patients with earlier-stage disease (P =.01 and P =.006, respectively). There was no correlation between cCD20 level and age, lymphocyte count, or white blood cell count. Using a recursive classification method, we found that patients with a cCD20 level more than 1875 nM/L had significantly shorter survival than those with cCD20 1875 nM/L or below (P =.01). The prognostic value of cCD20 was independent of Rai staging or hemoglobin level. Prospective evaluation is indicated to establish whether rituximab dosing should be adjusted according to cCD20 levels.
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4095, USA.
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Kim-anh
authors.initials: KA
authors.lastname: Do
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Helen
authors.initials: H
authors.lastname: Saffer
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Iman
authors.initials: I
authors.lastname: Jilani
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived; D000937:Antigen-Antibody Reactions; D018951:Antigens, CD20 / Q000097:blood* / Q000276:immunology; D001667:Binding, Competitive; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D008297:Male; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab