PXD064460

PXD064460 is an original dataset announced via ProteomeXchange.

Title	Investigation of LARP1 regulated cellular pathways in acute myeloid leukemia
Description	La-related protein 1 (LARP1) is an RNA-binding protein and downstream effector of mTOR and CDK9 signaling that regulates the translation of 5’-TOP mRNAs. While elevated LARP1 expression has been linked to poor prognosis in acute myeloid leukemia (AML), its mechanistic role remains unclear. Using CRISPR/Cas9-mediated LARP1 knockout and transcriptomic, translatomic, proteomic, and metabolomic analyses, we investigated LARP1’s role in AML. LARP1 loss impaired proliferation, clonogenicity, and tumor growth in xenografts, and enhanced sensitivity of AML cells to azacitidine and cytarabine. Polysome profiling and RNA sequencing revealed that LARP1 modulates a distinct set of transcripts involved in mitochondrial function, amino acid metabolism, and cell cycle regulation, independently of mTOR or CDK9. Proteomics analysis uncovered additional effects on immune signaling, lysosomal pathways, and protein stability, including changes not evident at the RNA level. Metabolomic profiling showed broad reprogramming of the arginine and creatine metabolic pathways and depletion of pyrimidine biosynthesis intermediates. Cytidine deaminase, a known resistance factor, was downregulated at both the transcript and protein levels upon LARP1 loss. These findings define LARP1 as a key integrator of translational regulation and metabolic control in AML, supporting leukemic cell survival and promoting drug resistance. Targeting LARP1 may uncover vulnerabilities not addressed by current antileukemia therapies.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:21:49.132.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Faull
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-30 12:56:03	ID requested
⏵ 1	2026-09-06 16:21:49	announced

10.1038/s41389-026-00623-3;

Nahotko DA, Lee B, Lopez Fajardo E, Baran AH, Filip SK, Faull PA, Bartom ET, Kocherginsky M, Gao P, Miska J, Saleiro D, Beauchamp EM, Platanias LC, Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML. Oncogenesis, 15(1):(2026) [pubmed]

submitter keyword: LARP1, acute myeloid leukemia

Elspeth Morrison Beauchamp
contact affiliation	Feinberg School of Medicine, Northwestern University, Chicago, USA
contact email	e-beauchamp@northwestern.edu
lab head
Peter Faull
contact affiliation	Northwestern University
contact email	peter.faull@northwestern.edu
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/2026/09/PXD064460

PRIDE project URI

• PRIDE
  1. PXD064460
     1. Label: PRIDE project
     2. Name: Investigation of LARP1 regulated cellular pathways in acute myeloid leukemia