Role of CD21 antigen in diffuse large B‐cell lymphoma and its clinical significance

Summary Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B‐...

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Veröffentlicht in:British journal of haematology 2004-11, Vol.127 (4), p.416-424
Hauptverfasser: Otsuka, Masaki, Yakushijin, Yoshihiro, Hamada, Makoto, Hato, Takaaki, Yasukawa, Masaki, Fujita, Sigeru
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container_issue 4
container_start_page 416
container_title British journal of haematology
container_volume 127
creator Otsuka, Masaki
Yakushijin, Yoshihiro
Hamada, Makoto
Hato, Takaaki
Yasukawa, Masaki
Fujita, Sigeru
description Summary Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B‐cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3·7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2·36, P 
doi_str_mv 10.1111/j.1365-2141.2004.05226.x
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Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B‐cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3·7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2·36, P &lt; 0·05). As a result of these clinical observations, we generated CD21‐overexpressed (CD21+) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector‐only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21+ transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P &lt; 0·05). Interestingly, all established CD21+ transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti‐CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2004.05226.x</identifier><identifier>PMID: 15521918</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; Biological and medical sciences ; CD21 ; Cell Division ; Cell Line, Tumor ; diffuse large B‐cell lymphoma ; Disease-Free Survival ; Female ; Flow Cytometry ; Hematologic and hematopoietic diseases ; Hematology ; homotypic aggregation ; Humans ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphoma, B-Cell - immunology ; Lymphoma, B-Cell - mortality ; Lymphoma, B-Cell - pathology ; Lymphoma, Large B-Cell, Diffuse - immunology ; Lymphoma, Large B-Cell, Diffuse - mortality ; Lymphoma, Large B-Cell, Diffuse - pathology ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Transplantation ; Phenotype ; Prognosis ; Receptors, Complement 3d - metabolism ; Transfection</subject><ispartof>British journal of haematology, 2004-11, Vol.127 (4), p.416-424</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. 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Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B‐cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3·7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2·36, P &lt; 0·05). As a result of these clinical observations, we generated CD21‐overexpressed (CD21+) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector‐only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21+ transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P &lt; 0·05). Interestingly, all established CD21+ transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti‐CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>CD21</subject><subject>Cell Division</subject><subject>Cell Line, Tumor</subject><subject>diffuse large B‐cell lymphoma</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>homotypic aggregation</subject><subject>Humans</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymphoma, B-Cell - immunology</subject><subject>Lymphoma, B-Cell - mortality</subject><subject>Lymphoma, B-Cell - pathology</subject><subject>Lymphoma, Large B-Cell, Diffuse - immunology</subject><subject>Lymphoma, Large B-Cell, Diffuse - mortality</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Middle Aged</subject><subject>Neoplasm Transplantation</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Receptors, Complement 3d - metabolism</subject><subject>Transfection</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMFu1DAQhi0EotvCKyALCW4JM3bs2AcOdCkUVAkJ0bPlJPbilZMs8UZ0bzwCz8iT4LArKnFiLjOWvxn9-gihCCXmerUtkUtRMKywZABVCYIxWd49IKu_Hw_JCgDqAqFSZ-Q8pS0AchD4mJyhEAw1qhW5_TxGR0dP128ZUjvsw8YNNAy0C97PydFop42jl79-_GxdjDQe-t3XsbcZ7WjYJ9rGMITWRprCZgg-j0PrnpBH3sbknp76Bbl9d_VlfV3cfHr_Yf3mpmgFV7JovdN11SjOwDc1eN1aofKzkgqZU053tqmlta5qEGuNXlRQQc2g0g3rUPML8vJ4dzeN32aX9qYPaclpBzfOycgaOJcMMvj8H3A7ztOQsxnUSmomZZ0hdYTaaUxpct7sptDb6WAQzOLdbM2i1yx6zeLd_PFu7vLqs9P9ueldd794Ep2BFyfApmzLT1lTSPecZFxwzTP3-sh9D9Ed_juAufx4vUz8N3NYnDU</recordid><startdate>200411</startdate><enddate>200411</enddate><creator>Otsuka, Masaki</creator><creator>Yakushijin, Yoshihiro</creator><creator>Hamada, Makoto</creator><creator>Hato, Takaaki</creator><creator>Yasukawa, Masaki</creator><creator>Fujita, Sigeru</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Publishing Ltd</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200411</creationdate><title>Role of CD21 antigen in diffuse large B‐cell lymphoma and its clinical significance</title><author>Otsuka, Masaki ; Yakushijin, Yoshihiro ; Hamada, Makoto ; Hato, Takaaki ; Yasukawa, Masaki ; Fujita, Sigeru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5386-cfe974b8320fb70f9ca58b8346812e8e9dab76aae4b11791f5404072049b2d193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>CD21</topic><topic>Cell Division</topic><topic>Cell Line, Tumor</topic><topic>diffuse large B‐cell lymphoma</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>homotypic aggregation</topic><topic>Humans</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymphoma, B-Cell - immunology</topic><topic>Lymphoma, B-Cell - mortality</topic><topic>Lymphoma, B-Cell - pathology</topic><topic>Lymphoma, Large B-Cell, Diffuse - immunology</topic><topic>Lymphoma, Large B-Cell, Diffuse - mortality</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Middle Aged</topic><topic>Neoplasm Transplantation</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Receptors, Complement 3d - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Otsuka, Masaki</creatorcontrib><creatorcontrib>Yakushijin, Yoshihiro</creatorcontrib><creatorcontrib>Hamada, Makoto</creatorcontrib><creatorcontrib>Hato, Takaaki</creatorcontrib><creatorcontrib>Yasukawa, Masaki</creatorcontrib><creatorcontrib>Fujita, Sigeru</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Otsuka, Masaki</au><au>Yakushijin, Yoshihiro</au><au>Hamada, Makoto</au><au>Hato, Takaaki</au><au>Yasukawa, Masaki</au><au>Fujita, Sigeru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of CD21 antigen in diffuse large B‐cell lymphoma and its clinical significance</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2004-11</date><risdate>2004</risdate><volume>127</volume><issue>4</issue><spage>416</spage><epage>424</epage><pages>416-424</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B‐cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3·7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2·36, P &lt; 0·05). As a result of these clinical observations, we generated CD21‐overexpressed (CD21+) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector‐only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21+ transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P &lt; 0·05). Interestingly, all established CD21+ transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti‐CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15521918</pmid><doi>10.1111/j.1365-2141.2004.05226.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Biological and medical sciences
CD21
Cell Division
Cell Line, Tumor
diffuse large B‐cell lymphoma
Disease-Free Survival
Female
Flow Cytometry
Hematologic and hematopoietic diseases
Hematology
homotypic aggregation
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma, B-Cell - immunology
Lymphoma, B-Cell - mortality
Lymphoma, B-Cell - pathology
Lymphoma, Large B-Cell, Diffuse - immunology
Lymphoma, Large B-Cell, Diffuse - mortality
Lymphoma, Large B-Cell, Diffuse - pathology
Male
Medical sciences
Mice
Mice, Inbred BALB C
Middle Aged
Neoplasm Transplantation
Phenotype
Prognosis
Receptors, Complement 3d - metabolism
Transfection
title Role of CD21 antigen in diffuse large B‐cell lymphoma and its clinical significance
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