Document Detail


Variability in B-cell antigen expression: implications for the treatment of B-cell lymphomas and leukemias with monoclonal antibodies.
MedLine Citation:
PMID:  11920265     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Antigen expression intensity is becoming important for decision-making in relation to monoclonal antibody therapy. By quantifying CD20, CD22 and CD52 expression on chronic lymphocytic leukemia and normal (control) B cells, over time. The effect of Interleukin-4 therapy on CD20 antigen intensity on B-CLL cells in vivo was also determined. METHODS: Lymphocytes were purified at weeks 0, 4 and 8 from five B-CLL patients, five healthy volunteers and seven B-CLL patients receiving IL-4 therapy. The number of antigen receptor sites was calculated in molecules of equivalent soluble fluorochrome using flow cytometry. RESULTS: The mean number of CD20 receptors at baseline was significantly lower on B-CLL cells compared to normal B cells (8160 vs 87 046; P<0.0001). Similar results were obtained for CD22 (8630 vs 27 647; P<0.01), but not for CD52 (371 303 vs 409 484; P = 0.54). When soluble fluorochrome values at weeks 4 and 8 were analysed as change in per cent from baseline (delta%), there was <10 delta% variability in CD20 expression on control B cells, but considerable variability (22.5-67.5 delta%) on B-CLL cells. Expression of CD22 in CLL and control B cells varied by <15 delta%. CD52 on CLL B cells showed slightly greater variability (+/-35 delta%) than that of CD22 (+/-15delta%), but less than that of CD20. IL-4 therapy did not consistently increase the CD20 expression on B-CLL cells in vivo. CONCLUSION: Our data confirm differences in intensity between different target antigens on B-CLL cells, and draws attention to the fact that a substantial variability may occur over time, which may influence clinical decision-making. Caution must be taken when interpreting in vitro results on cytokine-mediated receptor intensity up-regulation.
Authors:
E D Rossmann; J Lundin; R Lenkei; H Mellstedt; A Osterborg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The hematology journal : the official journal of the European Haematology Association / EHA     Volume:  2     ISSN:  1466-4860     ISO Abbreviation:  Hematol. J.     Publication Date:  2001  
Date Detail:
Created Date:  2002-03-28     Completed Date:  2002-06-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100965523     Medline TA:  Hematol J     Country:  England    
Other Details:
Languages:  eng     Pagination:  300-6     Citation Subset:  IM    
Affiliation:
Department of Oncology (Radiumhemmet), Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antibodies, Monoclonal / therapeutic use
Antigens, CD / biosynthesis
Antigens, CD20 / biosynthesis
Antigens, CD22
Antigens, CD5 / biosynthesis
Antigens, Differentiation, B-Lymphocyte / biosynthesis,  metabolism*
Antigens, Neoplasm / metabolism*
B-Lymphocytes / immunology,  pathology
Case-Control Studies
Cell Adhesion Molecules*
Female
Humans
Interleukin-4 / administration & dosage,  pharmacology
Lectins*
Leukemia, B-Cell / drug therapy,  immunology*,  pathology
Lymphoma, B-Cell / drug therapy,  immunology,  pathology
Male
Middle Aged
Time Factors
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antigens, CD20; 0/Antigens, CD22; 0/Antigens, CD5; 0/Antigens, Differentiation, B-Lymphocyte; 0/Antigens, Neoplasm; 0/CD22 protein, human; 0/Cell Adhesion Molecules; 0/Lectins; 207137-56-2/Interleukin-4

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