liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia
Lund University, Sweden.
Lund University, Sweden.
Lund University, Sweden.
Lund University, Sweden.
Show others and affiliations
2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 1, p. 213-221Article in journal (Refereed) Published
Abstract [en]

Mutations resulting in constitutive activation of signaling pathways that regulate ribosome biogenesis are among the most common genetic events in acute myeloid leukemia (AML). However, whether ribosome biogenesis presents as a therapeutic target to treat AML remains unexplored. Perturbations in ribosome biogenesis trigger the 5S ribonucleoprotein particle (RNP)-Mdm2-p53 ribosomal stress pathway, and induction of this pathway has been shown to have therapeutic efficacy in Myc-driven lymphoma. In the current study we address the physiological and therapeutic role of the 5S RNP-Mdm2-p53 pathway in AML. By utilizing mice that have defective ribosome biogenesis due to downregulation of ribosomal protein S19 (Rps19), we demonstrate that induction of the 5S RNP-Mdm2-p53 pathway significantly delays the initiation of AML. However, even a severe Rps19 deficiency that normally results in acute bone marrow failure has no consistent efficacy on already established disease. Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML. Our study suggests that induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway holds limited potential as a single-agent therapy in the treatment of AML.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 31, no 1, p. 213-221
National Category
Hematology
Identifiers
URN: urn:nbn:se:liu:diva-136370DOI: 10.1038/leu.2016.159ISI: 000394058700027PubMedID: 27256803OAI: oai:DiVA.org:liu-136370DiVA, id: diva2:1087796
Note

Funding Agencies|Swedish Childrens Cancer Society; Crafoord Foundation; Gunnar Nilsson Cancer Foundation; Swedish Research Council; Swedish Cancer Society; ERC Consolidator grant [615068]

Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2017-05-23

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Cammenga, Jörg
By organisation
Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Haematology
In the same journal
Leukemia
Hematology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 131 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf