YBX1 mediates translation of oncogenic transcripts to control cell competition in AML

  1. Perner, Florian ORCID logo
  2. Schnoeder, Tina M.
  3. Xiong, Yijun ORCID logo
  4. Jayavelu, Ashok Kumar
  5. Mashamba, Nomusa
  6. Santamaria, Nuria Tubio
  7. Huber, Nicolas
  8. Todorova, Kristina
  9. Hatton, Charlie ORCID logo
  10. Perner, Birgit
  11. Eifert, Theresa
  12. Murphy, Ciara
  13. Hartmann, Maximilian
  14. Hoell, Jessica I.
  15. Schröder, Nicolas
  16. Brandt, Sabine
  17. Hochhaus, Andreas
  18. Mertens, Peter R.
  19. Mann, Matthias
  20. Armstrong, Scott ORCID logo
  21. Mandinova, Anna
  22. Heidel, Florian ORCID logo

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1000 Titel
  • YBX1 mediates translation of oncogenic transcripts to control cell competition in AML
1000 Autor/in
  1. Perner, Florian |
  2. Schnoeder, Tina M. |
  3. Xiong, Yijun |
  4. Jayavelu, Ashok Kumar |
  5. Mashamba, Nomusa |
  6. Santamaria, Nuria Tubio |
  7. Huber, Nicolas |
  8. Todorova, Kristina |
  9. Hatton, Charlie |
  10. Perner, Birgit |
  11. Eifert, Theresa |
  12. Murphy, Ciara |
  13. Hartmann, Maximilian |
  14. Hoell, Jessica I. |
  15. Schröder, Nicolas |
  16. Brandt, Sabine |
  17. Hochhaus, Andreas |
  18. Mertens, Peter R. |
  19. Mann, Matthias |
  20. Armstrong, Scott |
  21. Mandinova, Anna |
  22. Heidel, Florian |
1000 Erscheinungsjahr 2021
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-08-31
1000 Erschienen in
1000 Quellenangabe
  • 36(2):426-437
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-021-01393-0 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807392/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
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 Proto-Oncogene Proteins c-myc/metabolism [MeSH]
lokal Y-Box-Binding Protein 1/genetics [MeSH]
lokal Janus Kinase 2/metabolism
lokal Mutation
lokal Janus Kinase 2/metabolism [MeSH]
lokal Leukemia, Myeloid, Acute/genetics
lokal Leukemia, Myeloid, Acute/metabolism [MeSH]
lokal Y-Box-Binding Protein 1/genetics
lokal Apoptosis [MeSH]
lokal Prognosis
lokal Mice
lokal Leukemia, Myeloid, Acute/metabolism
lokal Tumor Cells, Cultured [MeSH]
lokal Tumor Cells, Cultured
lokal Leukemia, Myeloid, Acute/genetics [MeSH]
lokal Proto-Oncogene Proteins c-myc/genetics
lokal Xenograft Model Antitumor Assays [MeSH]
lokal Biomarkers, Tumor/metabolism
lokal Cell Competition
lokal Cell Proliferation
lokal Humans
lokal Cell Proliferation [MeSH]
lokal Mutation [MeSH]
lokal Proto-Oncogene Proteins c-myc/metabolism
lokal Janus Kinase 2/genetics [MeSH]
lokal Humans [MeSH]
lokal Y-Box-Binding Protein 1/metabolism
lokal Apoptosis
lokal Animals [MeSH]
lokal Mice [MeSH]
lokal Biomarkers, Tumor/metabolism [MeSH]
lokal Proto-Oncogene Proteins c-myc/genetics [MeSH]
lokal Biomarkers, Tumor/genetics [MeSH]
lokal Janus Kinase 2/genetics
lokal Prognosis [MeSH]
lokal Y-Box-Binding Protein 1/metabolism [MeSH]
lokal Cell Competition [MeSH]
lokal Animals
lokal Leukemia, Myeloid, Acute/pathology
lokal Leukemia, Myeloid, Acute/pathology [MeSH]
lokal Biomarkers, Tumor/genetics
lokal Xenograft Model Antitumor Assays
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-1010-3321|https://frl.publisso.de/adhoc/uri/U2Nobm9lZGVyLCBUaW5hIE0u|https://orcid.org/0000-0001-6348-9649|https://frl.publisso.de/adhoc/uri/SmF5YXZlbHUsIEFzaG9rIEt1bWFy|https://frl.publisso.de/adhoc/uri/TWFzaGFtYmEsIE5vbXVzYQ==|https://frl.publisso.de/adhoc/uri/U2FudGFtYXJpYSwgTnVyaWEgVHViaW8=|https://frl.publisso.de/adhoc/uri/SHViZXIsIE5pY29sYXM=|https://frl.publisso.de/adhoc/uri/VG9kb3JvdmEsIEtyaXN0aW5h|https://orcid.org/0000-0001-9903-4291|https://frl.publisso.de/adhoc/uri/UGVybmVyLCBCaXJnaXQ=|https://frl.publisso.de/adhoc/uri/RWlmZXJ0LCBUaGVyZXNh|https://frl.publisso.de/adhoc/uri/TXVycGh5LCBDaWFyYQ==|https://frl.publisso.de/adhoc/uri/SGFydG1hbm4sIE1heGltaWxpYW4=|https://frl.publisso.de/adhoc/uri/SG9lbGwsIEplc3NpY2EgSS4=|https://frl.publisso.de/adhoc/uri/U2NocsO2ZGVyLCBOaWNvbGFz|https://frl.publisso.de/adhoc/uri/QnJhbmR0LCBTYWJpbmU=|https://frl.publisso.de/adhoc/uri/SG9jaGhhdXMsIEFuZHJlYXM=|https://frl.publisso.de/adhoc/uri/TWVydGVucywgUGV0ZXIgUi4=|https://frl.publisso.de/adhoc/uri/TWFubiwgTWF0dGhpYXM=|https://orcid.org/0000-0002-9099-4728|https://frl.publisso.de/adhoc/uri/TWFuZGlub3ZhLCBBbm5h|https://orcid.org/0000-0003-2438-1955
1000 Hinweis
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1000 @id frl:6443796.rdf
1000 Erstellt am 2023-04-27T10:50:24.530+0200
1000 Erstellt von 336
1000 beschreibt frl:6443796
1000 Zuletzt bearbeitet Wed May 08 08:36:45 CEST 2024
1000 Objekt bearb. Wed May 08 08:36:45 CEST 2024
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