Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour
Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM,...
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| Veröffentlicht in: | Leukemia 2001-07, Vol.15 (7), p.1127-1132 |
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| creator | BAKKUS, M. H. C ASOSINGH, K VANDERKERKEN, K THIELEMANS, K HAGEMEIJER, A DE RAEVE, H VAN CAMP, B |
| description | Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cmu region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM. |
| doi_str_mv | 10.1038/sj.leu.2402164 |
| format | Article |
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H. C ; ASOSINGH, K ; VANDERKERKEN, K ; THIELEMANS, K ; HAGEMEIJER, A ; DE RAEVE, H ; VAN CAMP, B</creator><creatorcontrib>BAKKUS, M. H. C ; ASOSINGH, K ; VANDERKERKEN, K ; THIELEMANS, K ; HAGEMEIJER, A ; DE RAEVE, H ; VAN CAMP, B</creatorcontrib><description>Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cmu region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2402164</identifier><identifier>PMID: 11455984</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Amino Acid Sequence ; Animal models ; Animals ; Antigens ; Base Sequence ; Biological and medical sciences ; Bone marrow ; Cells ; Chromosomes ; Cloning ; Hematologic and hematopoietic diseases ; Immunoglobulin A ; Immunoglobulin A - analysis ; Immunoglobulin Class Switching ; Immunoglobulin G ; Immunoglobulin G - analysis ; Immunoglobulin M ; Immunoglobulin M - analysis ; Immunology ; In Situ Hybridization, Fluorescence ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Multiple myeloma ; Multiple Myeloma - genetics ; Multiple Myeloma - immunology ; Mutation ; Polymerase Chain Reaction ; Stroma ; Switching ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Leukemia, 2001-07, Vol.15 (7), p.1127-1132</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jul 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-77f90aa5fda18bd7434fe55c732c6f80ef8e37f3d2932bdb4f01206447a082f83</citedby><cites>FETCH-LOGICAL-c407t-77f90aa5fda18bd7434fe55c732c6f80ef8e37f3d2932bdb4f01206447a082f83</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=14080404$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11455984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BAKKUS, M. H. C</creatorcontrib><creatorcontrib>ASOSINGH, K</creatorcontrib><creatorcontrib>VANDERKERKEN, K</creatorcontrib><creatorcontrib>THIELEMANS, K</creatorcontrib><creatorcontrib>HAGEMEIJER, A</creatorcontrib><creatorcontrib>DE RAEVE, H</creatorcontrib><creatorcontrib>VAN CAMP, B</creatorcontrib><title>Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cmu region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM.</description><subject>Amino Acid Sequence</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Cells</subject><subject>Chromosomes</subject><subject>Cloning</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin A - analysis</subject><subject>Immunoglobulin Class Switching</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - analysis</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulin M - analysis</subject><subject>Immunology</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Sequence Data</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - immunology</subject><subject>Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>Stroma</subject><subject>Switching</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqF0sFu1DAQANAIgehSuHJEFghuWcaOHTu9VVUpK7XiUs6R44y3XiX2YieF_R5-tC6NKEJCnOYwb2Y0mimK1xTWFCr1Me3WA85rxoHRmj8pVpTLuhRC0KfFCpSSZd0wflS8SGkHcJ-snxdHlHIhGsVXxc-rAw5h1MSlMB32WKbvbjI35FZHp_2UiPNkukEyztF5JOKajEvBGHocTgjeuh69waz09Du52V4R7fscTwn-2EdMyfktSXNnhuAxEaM9CdFtndcTEhvD-GvMZnvxp5_mMczxZfHM6iHhqyUeF18_nV-ffS4vv1xszk4vS8NBTqWUtgGthe01VV0vecUtCmFkxUxtFaBVWElb9aypWNd33AJlUHMuNShmVXVcfHjou4_h24xpakeXDA6D9hjm1EoKgjd1819IFZWMK5nhu7_gLu_j8xItq7mQkM8BWb39p2IgmKC0zmj9gEwMKUW07T66UcdDS6G9f4U27dr8Cu3yCrngzdJ17kbsH_ly-wzeL0AnowcbtTcuPToOCjjw6g7Alr4b</recordid><startdate>20010701</startdate><enddate>20010701</enddate><creator>BAKKUS, M. 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C</creator><creator>ASOSINGH, K</creator><creator>VANDERKERKEN, K</creator><creator>THIELEMANS, K</creator><creator>HAGEMEIJER, A</creator><creator>DE RAEVE, H</creator><creator>VAN CAMP, B</creator><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20010701</creationdate><title>Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour</title><author>BAKKUS, M. H. C ; ASOSINGH, K ; VANDERKERKEN, K ; THIELEMANS, K ; HAGEMEIJER, A ; DE RAEVE, H ; VAN CAMP, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-77f90aa5fda18bd7434fe55c732c6f80ef8e37f3d2932bdb4f01206447a082f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antigens</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Bone marrow</topic><topic>Cells</topic><topic>Chromosomes</topic><topic>Cloning</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin A - analysis</topic><topic>Immunoglobulin Class Switching</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - analysis</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulin M - analysis</topic><topic>Immunology</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Leukemia</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Sequence Data</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - immunology</topic><topic>Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Stroma</topic><topic>Switching</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BAKKUS, M. H. C</creatorcontrib><creatorcontrib>ASOSINGH, K</creatorcontrib><creatorcontrib>VANDERKERKEN, K</creatorcontrib><creatorcontrib>THIELEMANS, K</creatorcontrib><creatorcontrib>HAGEMEIJER, A</creatorcontrib><creatorcontrib>DE RAEVE, H</creatorcontrib><creatorcontrib>VAN CAMP, B</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>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BAKKUS, M. H. C</au><au>ASOSINGH, K</au><au>VANDERKERKEN, K</au><au>THIELEMANS, K</au><au>HAGEMEIJER, A</au><au>DE RAEVE, H</au><au>VAN CAMP, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2001-07-01</date><risdate>2001</risdate><volume>15</volume><issue>7</issue><spage>1127</spage><epage>1132</epage><pages>1127-1132</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>Isotype-switch variants can easily be detected in a significant proportion of multiple myeloma (MM) patients. The biological significance of these isotype-switch variants remains obscure. Therefore, we studied the appearance of these isotype-switch variants in two murine MM models, 5T2MM and 5T33MM, both of IgG isotype. With a MM-specific PCR assay we could detect isotype-switch variants in the bone marrow of both the 5T2MM and the 5T33MM bearing mice, reflecting again the close resemblance of this mouse model to the human MM. These isotype-switch variants were not found in an in vitro stroma-independent variant of the 5T33MM line. However, when this 5T33MMvitro line was injected into young syngeneic mice, isotype-switch variants appeared thereafter in the isolated tumour cells. These isotype-switch variants could only originate from the MM-IgG expressing cell since IgG subclones from the 5T33MMvitro line again gave rise to isotype-switch variants. The appearance of IgA cells can be explained by down-stream switching of IgG to IgA, while the emergence of IgM cells have to occur via trans-switching to the sister chromatid as the Cmu region is deleted from the CIS-chromosome. This study demonstrates that isotype-switch variants originate from the major tumour clone suggesting no role for the MM-IgM expressing cell as a pre-switch precursor MM cell. The appearance of isotype-switch variants should be considered as a rare but normal event now becoming visible due to the high number of clonal cells present in MM.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>11455984</pmid><doi>10.1038/sj.leu.2402164</doi><tpages>6</tpages></addata></record> |
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| ispartof | Leukemia, 2001-07, Vol.15 (7), p.1127-1132 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Amino Acid Sequence Animal models Animals Antigens Base Sequence Biological and medical sciences Bone marrow Cells Chromosomes Cloning Hematologic and hematopoietic diseases Immunoglobulin A Immunoglobulin A - analysis Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin G - analysis Immunoglobulin M Immunoglobulin M - analysis Immunology In Situ Hybridization, Fluorescence Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Mice Mice, Inbred C57BL Molecular Sequence Data Multiple myeloma Multiple Myeloma - genetics Multiple Myeloma - immunology Mutation Polymerase Chain Reaction Stroma Switching Tumor Cells, Cultured Tumors |
| title | Myeloma isotype-switch variants in the murine 5T myeloma model: evidence that myeloma IgM and IgA expressing subclones can originate from the IgG expressing tumour |
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