Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial

  1. Leypoldt, Lisa ORCID logo
  2. Besemer, Britta
  3. Asemissen, Anne Marie
  4. Hänel, Mathias
  5. Blau, Igor Wolfgang
  6. Görner, Martin
  7. Ko, Yon-Dschun
  8. Reinhardt, Hans Christian
  9. Staib, Peter
  10. Mann, Christoph
  11. Lutz, Raphael
  12. Munder, Markus
  13. Graeven, Ullrich ORCID logo
  14. Peceny, Rudolf
  15. Salwender, Hans ORCID logo
  16. Jauch, Anna
  17. Zago, Manola
  18. Benner, Axel ORCID logo
  19. Tichy, Diana
  20. Bokemeyer, Carsten
  21. Goldschmidt, Hartmut ORCID logo
  22. Weisel, Katja ORCID logo

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1000 Titel
  • Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial
1000 Autor/in
  1. Leypoldt, Lisa |
  2. Besemer, Britta |
  3. Asemissen, Anne Marie |
  4. Hänel, Mathias |
  5. Blau, Igor Wolfgang |
  6. Görner, Martin |
  7. Ko, Yon-Dschun |
  8. Reinhardt, Hans Christian |
  9. Staib, Peter |
  10. Mann, Christoph |
  11. Lutz, Raphael |
  12. Munder, Markus |
  13. Graeven, Ullrich |
  14. Peceny, Rudolf |
  15. Salwender, Hans |
  16. Jauch, Anna |
  17. Zago, Manola |
  18. Benner, Axel |
  19. Tichy, Diana |
  20. Bokemeyer, Carsten |
  21. Goldschmidt, Hartmut |
  22. Weisel, Katja |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-11-03
1000 Erschienen in
1000 Quellenangabe
  • 36(3):885-888
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-021-01431-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885414/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.
1000 Sacherschließung
lokal Dexamethasone/therapeutic use [MeSH]
lokal Female [MeSH]
lokal Letter
lokal Aged, 80 and over [MeSH]
lokal Aged [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Progression-Free Survival [MeSH]
lokal Middle Aged [MeSH]
lokal Antineoplastic Combined Chemotherapy Protocols/therapeutic use [MeSH]
lokal Male [MeSH]
lokal Antibodies, Monoclonal, Humanized/therapeutic use [MeSH]
lokal Myeloma
lokal Oligopeptides/therapeutic use [MeSH]
lokal Multiple Myeloma/drug therapy [MeSH]
lokal Lenalidomide/therapeutic use [MeSH]
lokal Phase II trials
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-9248-588X|https://frl.publisso.de/adhoc/uri/QmVzZW1lciwgQnJpdHRh|https://frl.publisso.de/adhoc/uri/QXNlbWlzc2VuLCBBbm5lIE1hcmll|https://frl.publisso.de/adhoc/uri/SMOkbmVsLCBNYXRoaWFz|https://frl.publisso.de/adhoc/uri/QmxhdSwgSWdvciBXb2xmZ2FuZw==|https://frl.publisso.de/adhoc/uri/R8O2cm5lciwgTWFydGlu|https://frl.publisso.de/adhoc/uri/S28sIFlvbi1Ec2NodW4=|https://frl.publisso.de/adhoc/uri/UmVpbmhhcmR0LCBIYW5zIENocmlzdGlhbg==|https://frl.publisso.de/adhoc/uri/U3RhaWIsIFBldGVy|https://frl.publisso.de/adhoc/uri/TWFubiwgQ2hyaXN0b3Bo|https://frl.publisso.de/adhoc/uri/THV0eiwgUmFwaGFlbA==|https://frl.publisso.de/adhoc/uri/TXVuZGVyLCBNYXJrdXM=|https://orcid.org/0000-0001-6082-7710|https://frl.publisso.de/adhoc/uri/UGVjZW55LCBSdWRvbGY=|https://orcid.org/0000-0001-7803-0814|https://frl.publisso.de/adhoc/uri/SmF1Y2gsIEFubmE=|https://frl.publisso.de/adhoc/uri/WmFnbywgTWFub2xh|https://orcid.org/0000-0002-7238-6956|https://frl.publisso.de/adhoc/uri/VGljaHksIERpYW5h|https://frl.publisso.de/adhoc/uri/Qm9rZW1leWVyLCBDYXJzdGVu|https://orcid.org/0000-0003-0961-0035|https://orcid.org/0000-0001-9422-6614
1000 Hinweis
  • DeepGreen-ID: d35c4bf49c6346a1897e0998e029eb36 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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1000 Erstellt am 2023-04-27T10:47:32.397+0200
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1000 Zuletzt bearbeitet Sat Oct 14 11:27:30 CEST 2023
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