| Autor: |
Daniel Sjövall, Sudip Ghosh, Narcis Fernandez-Fuentes, Talia Velasco-Hernandez, Anna Hogmalm, Pablo Menendez, Jenny Hansson, Carolina Guibentif, Pekka Jaako |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 43, Iss 11, Pp 114864- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114864 |
| Popis: |
Summary: Despite an advanced understanding of disease mechanisms, the current therapeutic regimen fails to cure most patients with acute myeloid leukemia (AML). In the present study, we address the role of ribosome assembly in leukemia cell function. We apply patient datasets and murine models to demonstrate that immature leukemia cells in mixed-lineage leukemia-rearranged AML are characterized by relatively high ribosome biogenesis and protein synthesis rates. Using a model with inducible regulation of ribosomal subunit joining, we show that defective ribosome assembly extends survival in mice with AML. Single-cell RNA sequencing and proteomic analyses reveal that leukemia cell adaptation to defective ribosome assembly is associated with an increase in ribosome biogenesis and deregulation of the transcription factor landscape. Finally, we demonstrate that defective ribosome assembly shows antileukemia efficacy in p53-deficient AML. Our study unveils the critical requirement of a high protein synthesis rate for leukemia progression and highlights ribosome assembly as a therapeutic target in AML. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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