Soluble CD200 Is Critical to Engraft Chronic Lymphocytic Leukemia Cells in Immunocompromised Mice
CD200 is a transmembrane molecule with an important immunoregulatory role that is overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the pl...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2012-10, Vol.72 (19), p.4931-4943 |
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| creator | WONG, Karrie K BRENNEMAN, Fred CHESNEY, Alden SPANER, David E GORCZYNSKI, Reginald M |
| description | CD200 is a transmembrane molecule with an important immunoregulatory role that is overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL as compared with healthy controls, and there was a significant correlation with CLL disease stage. Infusion of sCD200(hi) CLL plasma into severely immunocompromised NOD.SCIDγ(c)(null) (NSG) mice enhanced the engraftment of CLL splenocytes as compared with mice receiving sCD200(lo) normal plasma. CLL cells were detected in both the spleen and peritoneal cavity of animals for up to 75 days. Engraftment of CLL cells did not occur after infusion of CLL plasma depleted of sCD200 and was abolished in mice treated with anti-CD200 or OKT3 monoclonal antibody (mAb), suggesting a role for both sCD200 and T cells in CLL engraftment. Notably, anti-CD200 mAb was as effective as rituximab in eliminating engrafted CLL cells when administered 21 days after engraftment. Taken together, our findings point to sCD200 as a novel prognostic marker and therapeutic target for CLL. Furthermore, the humanized mouse model described here may prove valuable to preclinically assess new treatment regimens for CLL. |
| doi_str_mv | 10.1158/0008-5472.CAN-12-1390 |
| format | Article |
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In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL as compared with healthy controls, and there was a significant correlation with CLL disease stage. Infusion of sCD200(hi) CLL plasma into severely immunocompromised NOD.SCIDγ(c)(null) (NSG) mice enhanced the engraftment of CLL splenocytes as compared with mice receiving sCD200(lo) normal plasma. CLL cells were detected in both the spleen and peritoneal cavity of animals for up to 75 days. Engraftment of CLL cells did not occur after infusion of CLL plasma depleted of sCD200 and was abolished in mice treated with anti-CD200 or OKT3 monoclonal antibody (mAb), suggesting a role for both sCD200 and T cells in CLL engraftment. Notably, anti-CD200 mAb was as effective as rituximab in eliminating engrafted CLL cells when administered 21 days after engraftment. Taken together, our findings point to sCD200 as a novel prognostic marker and therapeutic target for CLL. Furthermore, the humanized mouse model described here may prove valuable to preclinically assess new treatment regimens for CLL.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-12-1390</identifier><identifier>PMID: 22875025</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Animals ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal, Murine-Derived - pharmacology ; Antigens, CD - blood ; Antigens, CD - immunology ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Cells, Cultured ; Female ; Hematologic and hematopoietic diseases ; Humans ; Immunocompromised Host - immunology ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Interleukin Receptor Common gamma Subunit - deficiency ; Interleukin Receptor Common gamma Subunit - genetics ; Interleukin Receptor Common gamma Subunit - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Middle Aged ; Muromonab-CD3 - pharmacology ; Pharmacology. Drug treatments ; Rituximab ; Spleen - drug effects ; Spleen - immunology ; Spleen - pathology ; Transplantation, Heterologous ; Treatment Outcome ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2012-10, Vol.72 (19), p.4931-4943</ispartof><rights>2015 INIST-CNRS</rights><rights>2012 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-582c68805e46b79241497ea4bf34f15f15b50f26badcdb722b476390302aefe73</citedby><cites>FETCH-LOGICAL-c438t-582c68805e46b79241497ea4bf34f15f15b50f26badcdb722b476390302aefe73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3360,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26429777$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22875025$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WONG, Karrie K</creatorcontrib><creatorcontrib>BRENNEMAN, Fred</creatorcontrib><creatorcontrib>CHESNEY, Alden</creatorcontrib><creatorcontrib>SPANER, David E</creatorcontrib><creatorcontrib>GORCZYNSKI, Reginald M</creatorcontrib><title>Soluble CD200 Is Critical to Engraft Chronic Lymphocytic Leukemia Cells in Immunocompromised Mice</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>CD200 is a transmembrane molecule with an important immunoregulatory role that is overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL as compared with healthy controls, and there was a significant correlation with CLL disease stage. Infusion of sCD200(hi) CLL plasma into severely immunocompromised NOD.SCIDγ(c)(null) (NSG) mice enhanced the engraftment of CLL splenocytes as compared with mice receiving sCD200(lo) normal plasma. CLL cells were detected in both the spleen and peritoneal cavity of animals for up to 75 days. Engraftment of CLL cells did not occur after infusion of CLL plasma depleted of sCD200 and was abolished in mice treated with anti-CD200 or OKT3 monoclonal antibody (mAb), suggesting a role for both sCD200 and T cells in CLL engraftment. Notably, anti-CD200 mAb was as effective as rituximab in eliminating engrafted CLL cells when administered 21 days after engraftment. Taken together, our findings point to sCD200 as a novel prognostic marker and therapeutic target for CLL. Furthermore, the humanized mouse model described here may prove valuable to preclinically assess new treatment regimens for CLL.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal, Murine-Derived - pharmacology</subject><subject>Antigens, CD - blood</subject><subject>Antigens, CD - immunology</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunocompromised Host - immunology</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Interleukin Receptor Common gamma Subunit - deficiency</subject><subject>Interleukin Receptor Common gamma Subunit - genetics</subject><subject>Interleukin Receptor Common gamma Subunit - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, Knockout</subject><subject>Mice, SCID</subject><subject>Middle Aged</subject><subject>Muromonab-CD3 - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rituximab</subject><subject>Spleen - drug effects</subject><subject>Spleen - immunology</subject><subject>Spleen - pathology</subject><subject>Transplantation, Heterologous</subject><subject>Treatment Outcome</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM9PwyAUgInRuDn9EzRcTLx0AoVCj6ZOXTL1oJ4JpdShbZnQHvbfS7M5k5e8R_K9H3wAXGI0x5iJW4SQSBjlZF7cvSSYJDjN0RGYYpaKhFPKjsH0wEzAWQhf8ckwYqdgQojgDBE2BerNNUPZGFjcE4TgMsDC295q1cDewUX36VXdw2LtXWc1XG3bzdrpbT_WZvg2rVWwME0ToO3gsm2HzmnXbrxrbTAVfLbanIOTWjXBXOzzDHw8LN6Lp2T1-rgs7laJpqnoEyaIzoRAzNCs5DmhmObcKFrWKa0xi1EyVJOsVJWuSk5ISXkWv5wiokxteDoDN7u5cfvPYEIv4w063qY644YgMRKEpFlOR5TtUO1dCN7UcuNtq_w2QnK0K0dzcjQno12JiRztxr6r_YqhbE116PrTGYHrPaBCVFh71Wkb_rmMkpxznv4CRCGBRQ</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>WONG, Karrie K</creator><creator>BRENNEMAN, Fred</creator><creator>CHESNEY, Alden</creator><creator>SPANER, David E</creator><creator>GORCZYNSKI, Reginald M</creator><general>American Association for Cancer Research</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>7X8</scope></search><sort><creationdate>20121001</creationdate><title>Soluble CD200 Is Critical to Engraft Chronic Lymphocytic Leukemia Cells in Immunocompromised Mice</title><author>WONG, Karrie K ; BRENNEMAN, Fred ; CHESNEY, Alden ; SPANER, David E ; GORCZYNSKI, Reginald M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-582c68805e46b79241497ea4bf34f15f15b50f26badcdb722b476390302aefe73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal, Murine-Derived - pharmacology</topic><topic>Antigens, CD - blood</topic><topic>Antigens, CD - immunology</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunocompromised Host - immunology</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Interleukin Receptor Common gamma Subunit - deficiency</topic><topic>Interleukin Receptor Common gamma Subunit - genetics</topic><topic>Interleukin Receptor Common gamma Subunit - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, Knockout</topic><topic>Mice, SCID</topic><topic>Middle Aged</topic><topic>Muromonab-CD3 - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rituximab</topic><topic>Spleen - drug effects</topic><topic>Spleen - immunology</topic><topic>Spleen - pathology</topic><topic>Transplantation, Heterologous</topic><topic>Treatment Outcome</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WONG, Karrie K</creatorcontrib><creatorcontrib>BRENNEMAN, Fred</creatorcontrib><creatorcontrib>CHESNEY, Alden</creatorcontrib><creatorcontrib>SPANER, David E</creatorcontrib><creatorcontrib>GORCZYNSKI, Reginald M</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>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WONG, Karrie K</au><au>BRENNEMAN, Fred</au><au>CHESNEY, Alden</au><au>SPANER, David E</au><au>GORCZYNSKI, Reginald M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Soluble CD200 Is Critical to Engraft Chronic Lymphocytic Leukemia Cells in Immunocompromised Mice</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>72</volume><issue>19</issue><spage>4931</spage><epage>4943</epage><pages>4931-4943</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>CD200 is a transmembrane molecule with an important immunoregulatory role that is overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL as compared with healthy controls, and there was a significant correlation with CLL disease stage. Infusion of sCD200(hi) CLL plasma into severely immunocompromised NOD.SCIDγ(c)(null) (NSG) mice enhanced the engraftment of CLL splenocytes as compared with mice receiving sCD200(lo) normal plasma. CLL cells were detected in both the spleen and peritoneal cavity of animals for up to 75 days. Engraftment of CLL cells did not occur after infusion of CLL plasma depleted of sCD200 and was abolished in mice treated with anti-CD200 or OKT3 monoclonal antibody (mAb), suggesting a role for both sCD200 and T cells in CLL engraftment. Notably, anti-CD200 mAb was as effective as rituximab in eliminating engrafted CLL cells when administered 21 days after engraftment. Taken together, our findings point to sCD200 as a novel prognostic marker and therapeutic target for CLL. Furthermore, the humanized mouse model described here may prove valuable to preclinically assess new treatment regimens for CLL.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>22875025</pmid><doi>10.1158/0008-5472.CAN-12-1390</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Animals Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Murine-Derived - pharmacology Antigens, CD - blood Antigens, CD - immunology Antineoplastic agents Antineoplastic Agents - pharmacology Biological and medical sciences Cells, Cultured Female Hematologic and hematopoietic diseases Humans Immunocompromised Host - immunology Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Interleukin Receptor Common gamma Subunit - deficiency Interleukin Receptor Common gamma Subunit - genetics Interleukin Receptor Common gamma Subunit - immunology Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukemia, Lymphocytic, Chronic, B-Cell - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Middle Aged Muromonab-CD3 - pharmacology Pharmacology. Drug treatments Rituximab Spleen - drug effects Spleen - immunology Spleen - pathology Transplantation, Heterologous Treatment Outcome Tumor Cells, Cultured Tumors |
| title | Soluble CD200 Is Critical to Engraft Chronic Lymphocytic Leukemia Cells in Immunocompromised Mice |
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