Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance

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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 β2-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.