Proteomics

Dataset Information

0

Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia


ABSTRACT: Despite the advanced understanding of disease mechanisms, the current therapeutic regimens fail to cure most patients with acute myeloid leukemia (AML). In the present study, we address the role of protein synthesis control in AML leukemia stem cell (LSC) function and leukemia propagation. We apply a murine model of mixed-lineage leukemia-rearranged AML to demonstrate that LSCs synthesize more proteins per hour compared with the bulk of leukemia. Using a genetic model that permits inducible and graded regulation of ribosomal subunit joining, we show that defective ribosome assembly leads to a significant survival advantage by selectively eradicating LSCs but not normal hematopoietic stem and progenitor cells. Finally, transcriptomic and proteomic analyses identify a rare subset of LSCs with immature stem cell signature and high ribosome content that underlies the resistance to defective ribosome assembly. Collectively, our study unveils a critical requirement of high protein synthesis rate for LSC function, highlighting ribosome assembly as a therapeutic target in AML.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Sudip Ghosh  

LAB HEAD: Jenny Hansson

PROVIDER: PXD038318 | Pride | 2024-10-08

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
220708_eif6_TMT10_F01_of_08_R1.raw Raw
220708_eif6_TMT10_F01_of_08_R2.raw Raw
220708_eif6_TMT10_F02_of_08_R1.raw Raw
220708_eif6_TMT10_F02_of_08_R2.raw Raw
220708_eif6_TMT10_F03_of_08_R1.raw Raw
Items per page:
1 - 5 of 19
altmetric image

Publications

Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia.

Sjövall Daniel D   Ghosh Sudip S   Fernandez-Fuentes Narcis N   Velasco-Hernandez Talia T   Hogmalm Anna A   Menendez Pablo P   Hansson Jenny J   Guibentif Carolina C   Jaako Pekka P  

Cell reports 20241015 11


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  ...[more]

Similar Datasets

2023-03-01 | E-MTAB-11976 | biostudies-arrayexpress
2023-02-06 | GSE185991 | GEO
2023-02-06 | GSE185834 | GEO
2023-02-06 | GSE185824 | GEO
2024-06-13 | PXD042796 | Pride
2015-01-15 | E-GEOD-64545 | biostudies-arrayexpress
2020-10-10 | GSE159322 | GEO
2020-10-10 | GSE159321 | GEO
2020-10-10 | GSE159319 | GEO
2009-02-21 | E-GEOD-13692 | biostudies-arrayexpress