PXD038318

PXD038318 is an original dataset announced via ProteomeXchange.

Title	Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-23
AnnouncementXML	Submission_2024-10-23_03:02:41.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sudip Ghosh
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-23 04:43:58	ID requested
1	2024-10-08 01:05:48	announced
2	2024-10-22 07:00:53	announced	2024-10-22: Updated project metadata.
⏵ 3	2024-10-23 03:02:41	announced	2024-10-23: Updated project metadata.

10.1016/j.celrep.2024.114864;

Sj, ö, vall D, Ghosh S, Fernandez-Fuentes N, Velasco-Hernandez T, Hogmalm A, Menendez P, Hansson J, Guibentif C, Jaako P, Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia. Cell Rep, 43(11):114864(2024) [pubmed]

submitter keyword: AML, Ribosome, LSC

Jenny Hansson
contact affiliation	Proteomic Hematology, Division of Molecular Hematology, Lund Stem Cell Center, Lund University
contact email	jenny.hansson@med.lu.se
lab head
Sudip Ghosh
contact affiliation	Proteomic Hematology, Department of Experimental Medical Science, Lund Stem Cell Center, Lund University
contact email	sudip.ghosh@med.lu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD038318

PRIDE project URI

• PRIDE
  1. PXD038318
     1. Label: PRIDE project
     2. Name: Defective ribosome assembly impairs leukemia progression in a murine model of acute myeloid leukemia