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• W1755571255 abstract "// Eva-Maria Nichols 1 , Rachel Jones 1 , Rachael Watson 1 , Chris J. Pepper 2, * , Chris Fegan 2, * , Kevin J. Marchbank 1, * 1 Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK 2 Institute of Cancer & Genetics, Cardiff University School of Medicine, Cardiff, UK * These authors have contributed equally to this work Correspondence to: Kevin J. Marchbank, e-mail: kevin.marchbank@ncl.ac.uk Keywords: CLL, poor prognosis, CD21, complement, B cell Received: May 19, 2015      Accepted: September 02, 2015      Published: October 03, 2015 ABSTRACT B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR signaling and autoimmune complications. Complement modulates B-cell function via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that CD21 contributes to BCR signaling and participates in the autoimmunity associated with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2, CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that expressed on B-cells from age-matched controls ( P < 0.0001) and was inversely correlated with soluble CD21 ( r 2 = –0.41). We found no evidence of autoantibody to any complement regulator. Low CD21 expression correlated to prognostic subsets of CLL patients, i.e. cases with unmutated IGHV genes ( P = 0.0006), high CD38 ( P = 0.02) and high ZAP70 expression ( P = 0.0017). Low CD21 expression was inversely correlated to the levels of phosphotyrosine induced in CLL cells following BCR ligation with αIgM ( r 2 = –0.21). Importantly, lower CD21 expression was also predictive for reduced overall survival ( P = 0.005; HR = 2.7). In conclusion, we showed that reduced expression of CD21 on CLL B-cells appears functionally relevant and was associated with poor clinical outcomes." @default.
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• W1755571255 date "2015-10-03" @default.
• W1755571255 modified "2023-09-27" @default.
• W1755571255 title "A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL" @default.
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• W1755571255 doi "https://doi.org/10.18632/oncotarget.5404" @default.
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