Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients
Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the...
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| Veröffentlicht in: | Blood cancer journal (New York) 2019-01, Vol.9 (2), p.13-13, Article 13 |
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| creator | Kriegsmann, Katharina Baertsch, Marc-Andrea Awwad, Mohamed H. S. Merz, Maximilian Hose, Dirk Seckinger, Anja Jauch, Anna Becker, Natalia Benner, Axel Raab, Marc S. Hillengass, Jens Bertsch, Uta Dürig, Jan Salwender, Hans Jürgen Hänel, Mathias Fenk, Roland Munder, Markus Weisel, Katja Müller-Tidow, Carsten Goldschmidt, Hartmut Hundemer, Michael |
| description | Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells. |
| doi_str_mv | 10.1038/s41408-019-0174-z |
| format | Article |
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S. ; Merz, Maximilian ; Hose, Dirk ; Seckinger, Anja ; Jauch, Anna ; Becker, Natalia ; Benner, Axel ; Raab, Marc S. ; Hillengass, Jens ; Bertsch, Uta ; Dürig, Jan ; Salwender, Hans Jürgen ; Hänel, Mathias ; Fenk, Roland ; Munder, Markus ; Weisel, Katja ; Müller-Tidow, Carsten ; Goldschmidt, Hartmut ; Hundemer, Michael</creator><creatorcontrib>Kriegsmann, Katharina ; Baertsch, Marc-Andrea ; Awwad, Mohamed H. S. ; Merz, Maximilian ; Hose, Dirk ; Seckinger, Anja ; Jauch, Anna ; Becker, Natalia ; Benner, Axel ; Raab, Marc S. ; Hillengass, Jens ; Bertsch, Uta ; Dürig, Jan ; Salwender, Hans Jürgen ; Hänel, Mathias ; Fenk, Roland ; Munder, Markus ; Weisel, Katja ; Müller-Tidow, Carsten ; Goldschmidt, Hartmut ; Hundemer, Michael</creatorcontrib><description>Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.</description><identifier>ISSN: 2044-5385</identifier><identifier>EISSN: 2044-5385</identifier><identifier>DOI: 10.1038/s41408-019-0174-z</identifier><identifier>PMID: 30696815</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/1 ; 14/32 ; 631/67/1059/2325 ; 692/699/1541/1990/804 ; Adaptor Proteins, Signal Transducing - metabolism ; Adult ; Aged ; Biomarkers, Tumor ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cytogenetic Analysis ; Female ; Gene Expression ; Hematology ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - diagnosis ; Multiple Myeloma - drug therapy ; Multiple Myeloma - genetics ; Multiple Myeloma - metabolism ; Neoplasm Staging ; Oncology ; Polyploidy ; Protein Binding ; Proteins</subject><ispartof>Blood cancer journal (New York), 2019-01, Vol.9 (2), p.13-13, Article 13</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-4f89eb3d29ffcc7c3bf2ffa545721d1d968e8d8ccfc1685d9f994a4de7b2802a3</citedby><cites>FETCH-LOGICAL-c470t-4f89eb3d29ffcc7c3bf2ffa545721d1d968e8d8ccfc1685d9f994a4de7b2802a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351644/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351644/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30696815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kriegsmann, Katharina</creatorcontrib><creatorcontrib>Baertsch, Marc-Andrea</creatorcontrib><creatorcontrib>Awwad, Mohamed H. S.</creatorcontrib><creatorcontrib>Merz, Maximilian</creatorcontrib><creatorcontrib>Hose, Dirk</creatorcontrib><creatorcontrib>Seckinger, Anja</creatorcontrib><creatorcontrib>Jauch, Anna</creatorcontrib><creatorcontrib>Becker, Natalia</creatorcontrib><creatorcontrib>Benner, Axel</creatorcontrib><creatorcontrib>Raab, Marc S.</creatorcontrib><creatorcontrib>Hillengass, Jens</creatorcontrib><creatorcontrib>Bertsch, Uta</creatorcontrib><creatorcontrib>Dürig, Jan</creatorcontrib><creatorcontrib>Salwender, Hans Jürgen</creatorcontrib><creatorcontrib>Hänel, Mathias</creatorcontrib><creatorcontrib>Fenk, Roland</creatorcontrib><creatorcontrib>Munder, Markus</creatorcontrib><creatorcontrib>Weisel, Katja</creatorcontrib><creatorcontrib>Müller-Tidow, Carsten</creatorcontrib><creatorcontrib>Goldschmidt, Hartmut</creatorcontrib><creatorcontrib>Hundemer, Michael</creatorcontrib><title>Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients</title><title>Blood cancer journal (New York)</title><addtitle>Blood Cancer Journal</addtitle><addtitle>Blood Cancer J</addtitle><description>Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.</description><subject>14/1</subject><subject>14/32</subject><subject>631/67/1059/2325</subject><subject>692/699/1541/1990/804</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers, Tumor</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cytogenetic Analysis</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - diagnosis</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - metabolism</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Polyploidy</subject><subject>Protein Binding</subject><subject>Proteins</subject><issn>2044-5385</issn><issn>2044-5385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUFrHSEUhYfS0oQ0P6CbInTTzaQ6ozO6KZRH2xQC3SRrcfT6nsHRqc4kmfz6-nhJmhYiiBfud8_1cKrqPcFnBLf8c6aEYl5jIsrtaX3_qjpuMKU1azl7_aw-qk5zvsblsI4IIt5WRy3uRMcJO66WDSQYfAz14IJxYYumFGdwISO4mxLk7GJAHm7AZ6RjSuDVDOjWzTu0WydIxk0-OrMiF1CAW78i49Q2xAwGjYufSxvQuIKPo0KTmh2EOb-r3ljlM5w-vCfV1fdvl5vz-uLXj5-brxe1pj2ea2q5gKE1jbBW6163g22sVYyyviGGmOIBuOFaW006zoywQlBFDfRDw3Gj2pPqy0F3WoYRjC67k_JySm5UaZVROflvJ7id3MYb2bWMdJQWgU8PAin-XiDPcnRZg_cqQFyybEgvKOtavEc__odexyWFYm9PNV3XtxwXihwonWLOCezTZwiW-1zlIVdZcpX7XOV9mfnw3MXTxGOKBWgOQC6tsIX0d_XLqn8AtoCzIQ</recordid><startdate>20190129</startdate><enddate>20190129</enddate><creator>Kriegsmann, Katharina</creator><creator>Baertsch, Marc-Andrea</creator><creator>Awwad, Mohamed H. 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S. ; Merz, Maximilian ; Hose, Dirk ; Seckinger, Anja ; Jauch, Anna ; Becker, Natalia ; Benner, Axel ; Raab, Marc S. ; Hillengass, Jens ; Bertsch, Uta ; Dürig, Jan ; Salwender, Hans Jürgen ; Hänel, Mathias ; Fenk, Roland ; Munder, Markus ; Weisel, Katja ; Müller-Tidow, Carsten ; Goldschmidt, Hartmut ; Hundemer, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-4f89eb3d29ffcc7c3bf2ffa545721d1d968e8d8ccfc1685d9f994a4de7b2802a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>14/1</topic><topic>14/32</topic><topic>631/67/1059/2325</topic><topic>692/699/1541/1990/804</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers, Tumor</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cytogenetic Analysis</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - diagnosis</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - metabolism</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Polyploidy</topic><topic>Protein Binding</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kriegsmann, Katharina</creatorcontrib><creatorcontrib>Baertsch, Marc-Andrea</creatorcontrib><creatorcontrib>Awwad, Mohamed H. 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S.</au><au>Merz, Maximilian</au><au>Hose, Dirk</au><au>Seckinger, Anja</au><au>Jauch, Anna</au><au>Becker, Natalia</au><au>Benner, Axel</au><au>Raab, Marc S.</au><au>Hillengass, Jens</au><au>Bertsch, Uta</au><au>Dürig, Jan</au><au>Salwender, Hans Jürgen</au><au>Hänel, Mathias</au><au>Fenk, Roland</au><au>Munder, Markus</au><au>Weisel, Katja</au><au>Müller-Tidow, Carsten</au><au>Goldschmidt, Hartmut</au><au>Hundemer, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients</atitle><jtitle>Blood cancer journal (New York)</jtitle><stitle>Blood Cancer Journal</stitle><addtitle>Blood Cancer J</addtitle><date>2019-01-29</date><risdate>2019</risdate><volume>9</volume><issue>2</issue><spage>13</spage><epage>13</epage><pages>13-13</pages><artnum>13</artnum><issn>2044-5385</issn><eissn>2044-5385</eissn><abstract>Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30696815</pmid><doi>10.1038/s41408-019-0174-z</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 14/1 14/32 631/67/1059/2325 692/699/1541/1990/804 Adaptor Proteins, Signal Transducing - metabolism Adult Aged Biomarkers, Tumor Biomedical and Life Sciences Biomedicine Cancer Research Carrier Proteins - genetics Carrier Proteins - metabolism Cytogenetic Analysis Female Gene Expression Hematology Humans Immunophenotyping Male Middle Aged Multiple myeloma Multiple Myeloma - diagnosis Multiple Myeloma - drug therapy Multiple Myeloma - genetics Multiple Myeloma - metabolism Neoplasm Staging Oncology Polyploidy Protein Binding Proteins |
| title | Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients |
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