Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia
We examined isolated leukemia B cells of patients with chronic lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed...
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| Veröffentlicht in: | Blood 2002-12, Vol.100 (13), p.4609-4614 |
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| creator | Chen, Liguang Widhopf, George Huynh, Lang Rassenti, Laura Rai, Kanti R. Weiss, Arthur Kipps, Thomas J. |
| description | We examined isolated leukemia B cells of patients with chronic lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed by normal blood T cells. In contrast, CLL B cells that had mutated immunoglobulin variable V genes, or that had low-level expression of CD38, generally did not express detectable amounts of ZAP-70 protein. Leukemia cells from identical twins with CLL were found discordant for expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72Syk, than did similar stimulation of CLL cells that did not express ZAP-70. Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. These data indicate that expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express nonmutated immunoglobulin receptors. |
| doi_str_mv | 10.1182/blood-2002-06-1683 |
| format | Article |
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CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed by normal blood T cells. In contrast, CLL B cells that had mutated immunoglobulin variable V genes, or that had low-level expression of CD38, generally did not express detectable amounts of ZAP-70 protein. Leukemia cells from identical twins with CLL were found discordant for expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72Syk, than did similar stimulation of CLL cells that did not express ZAP-70. Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. These data indicate that expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express nonmutated immunoglobulin receptors.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2002-06-1683</identifier><identifier>PMID: 12393534</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; B-Lymphocytes - immunology ; B-Lymphocytes - metabolism ; Biological and medical sciences ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Diseases in Twins ; Enzyme Precursors - metabolism ; Gene Expression Regulation, Leukemic ; Gene Rearrangement, B-Lymphocyte ; Genes, Immunoglobulin ; Hematologic and hematopoietic diseases ; Humans ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Variable Region - genetics ; Intracellular Signaling Peptides and Proteins ; Leukemia, Lymphocytic, Chronic, B-Cell - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Neoplasm Proteins - biosynthesis ; Neoplasm Proteins - genetics ; Neoplasm Proteins - physiology ; Phosphorylation ; Protein Processing, Post-Translational ; Protein-Tyrosine Kinases - biosynthesis ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Protein-Tyrosine Kinases - physiology ; Receptors, Antigen, B-Cell - immunology ; Signal Transduction ; Syk Kinase ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; ZAP-70 Protein-Tyrosine Kinase</subject><ispartof>Blood, 2002-12, Vol.100 (13), p.4609-4614</ispartof><rights>2002 American Society of Hematology</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-955186e44c7defb83b91f8abbf75c78493415f80ff669b76d7400350483d14be3</citedby><cites>FETCH-LOGICAL-c426t-955186e44c7defb83b91f8abbf75c78493415f80ff669b76d7400350483d14be3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14388348$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12393534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Liguang</creatorcontrib><creatorcontrib>Widhopf, George</creatorcontrib><creatorcontrib>Huynh, Lang</creatorcontrib><creatorcontrib>Rassenti, Laura</creatorcontrib><creatorcontrib>Rai, Kanti R.</creatorcontrib><creatorcontrib>Weiss, Arthur</creatorcontrib><creatorcontrib>Kipps, Thomas J.</creatorcontrib><title>Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia</title><title>Blood</title><addtitle>Blood</addtitle><description>We examined isolated leukemia B cells of patients with chronic lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed by normal blood T cells. In contrast, CLL B cells that had mutated immunoglobulin variable V genes, or that had low-level expression of CD38, generally did not express detectable amounts of ZAP-70 protein. Leukemia cells from identical twins with CLL were found discordant for expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72Syk, than did similar stimulation of CLL cells that did not express ZAP-70. Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. These data indicate that expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express nonmutated immunoglobulin receptors.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Diseases in Twins</subject><subject>Enzyme Precursors - metabolism</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Gene Rearrangement, B-Lymphocyte</subject><subject>Genes, Immunoglobulin</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - physiology</subject><subject>Phosphorylation</subject><subject>Protein Processing, Post-Translational</subject><subject>Protein-Tyrosine Kinases - biosynthesis</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Protein-Tyrosine Kinases - physiology</subject><subject>Receptors, Antigen, B-Cell - immunology</subject><subject>Signal Transduction</subject><subject>Syk Kinase</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>ZAP-70 Protein-Tyrosine Kinase</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi1URJeFP8AB-VJuAX8ldiQubVU-pEpwgAsXy3HGXdMkDp5sYf89DrtSb5zGM3pm_Ooh5BVnbzk34l03pNRXgjFRsabijZFPyIbXwlRlxM7IhrEyV63m5-Q54k_GuJKifkbOuZCtrKXakPubP3MGxJgmmgL9cfm10oxGpA4x-egW6OnvuOxonHwGh6W9qjwMA83gYV5SphjvJjfE6a4w1O9ymqKnw2Gcd8kflvUN-3sYo3tBngY3ILw81S35_uHm2_Wn6vbLx8_Xl7eVV6JZqrauuWlAKa97CJ2RXcuDcV0XdO21Ua1UvA6GhdA0baebXivGZM2UkT1XHcgteXO8O-f0aw-42DHimtlNkPZotdC8_KQKKI6gzwkxQ7BzjqPLB8uZXRXbf4rtqtiyxq6Ky9Lr0_V9N0L_uHJyWoCLE-DQuyFkN_mIj5ySxsgSdkveHzkoLh4iZIs-wuShj8XtYvsU_5fjLx4jmcY</recordid><startdate>20021215</startdate><enddate>20021215</enddate><creator>Chen, Liguang</creator><creator>Widhopf, George</creator><creator>Huynh, Lang</creator><creator>Rassenti, Laura</creator><creator>Rai, Kanti R.</creator><creator>Weiss, Arthur</creator><creator>Kipps, Thomas J.</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>20021215</creationdate><title>Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia</title><author>Chen, Liguang ; Widhopf, George ; Huynh, Lang ; Rassenti, Laura ; Rai, Kanti R. ; Weiss, Arthur ; Kipps, Thomas J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-955186e44c7defb83b91f8abbf75c78493415f80ff669b76d7400350483d14be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>Diseases in Twins</topic><topic>Enzyme Precursors - metabolism</topic><topic>Gene Expression Regulation, Leukemic</topic><topic>Gene Rearrangement, B-Lymphocyte</topic><topic>Genes, Immunoglobulin</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Neoplasm Proteins - biosynthesis</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - physiology</topic><topic>Phosphorylation</topic><topic>Protein Processing, Post-Translational</topic><topic>Protein-Tyrosine Kinases - biosynthesis</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Protein-Tyrosine Kinases - physiology</topic><topic>Receptors, Antigen, B-Cell - immunology</topic><topic>Signal Transduction</topic><topic>Syk Kinase</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>ZAP-70 Protein-Tyrosine Kinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Liguang</creatorcontrib><creatorcontrib>Widhopf, George</creatorcontrib><creatorcontrib>Huynh, Lang</creatorcontrib><creatorcontrib>Rassenti, Laura</creatorcontrib><creatorcontrib>Rai, Kanti R.</creatorcontrib><creatorcontrib>Weiss, Arthur</creatorcontrib><creatorcontrib>Kipps, Thomas J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Liguang</au><au>Widhopf, George</au><au>Huynh, Lang</au><au>Rassenti, Laura</au><au>Rai, Kanti R.</au><au>Weiss, Arthur</au><au>Kipps, Thomas J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2002-12-15</date><risdate>2002</risdate><volume>100</volume><issue>13</issue><spage>4609</spage><epage>4614</epage><pages>4609-4614</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>We examined isolated leukemia B cells of patients with chronic lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed by normal blood T cells. In contrast, CLL B cells that had mutated immunoglobulin variable V genes, or that had low-level expression of CD38, generally did not express detectable amounts of ZAP-70 protein. Leukemia cells from identical twins with CLL were found discordant for expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72Syk, than did similar stimulation of CLL cells that did not express ZAP-70. Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. These data indicate that expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express nonmutated immunoglobulin receptors.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>12393534</pmid><doi>10.1182/blood-2002-06-1683</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy B-Lymphocytes - immunology B-Lymphocytes - metabolism Biological and medical sciences Bone marrow, stem cells transplantation. Graft versus host reaction Diseases in Twins Enzyme Precursors - metabolism Gene Expression Regulation, Leukemic Gene Rearrangement, B-Lymphocyte Genes, Immunoglobulin Hematologic and hematopoietic diseases Humans Immunoglobulin Heavy Chains - genetics Immunoglobulin Variable Region - genetics Intracellular Signaling Peptides and Proteins Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Neoplasm Proteins - biosynthesis Neoplasm Proteins - genetics Neoplasm Proteins - physiology Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinases - biosynthesis Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Protein-Tyrosine Kinases - physiology Receptors, Antigen, B-Cell - immunology Signal Transduction Syk Kinase Transfusions. Complications. Transfusion reactions. Cell and gene therapy ZAP-70 Protein-Tyrosine Kinase |
| title | Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia |
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