PXD058648

PXD058648 is an original dataset announced via ProteomeXchange.

Title	Bone Marrow Mesenchymal Stromal Cells Support Translation in Refractory Acute Myeloid Leukemia
Description	In acute myeloid leukemia (AML), malignant cells surviving chemotherapy rely on high mRNA translation and their microenvironmental metabolic support to drive relapse. However, the role of translational reprogramming in the niche is unclear. Here we found that relapsing AML cells increase translation in their bone marrow (BM) niches, where BM mesenchymal stromal cells (BMSCs) become a source of eIF4A-cap-dependent translation machinery that is transferred to AML cells via extracellular vesicles (EVs), to meet their translational demands. In two independent models of highly chemo-resistant AML driven by MLL-AF9 or FLT3-ITD;NPMc mutations, protein synthesis levels increase in refractory AML dependently on nestin+ BMSCs. Inhibiting cap-dependent translation in BMSCs abolishes their chemoprotective ability, while EVs from BMSCs carrying eIF4A boost AML cell translation and survival. Consequently, eIF4A inhibition synergizes with conventional chemotherapy. Together, these results suggest that AML cells rely on BMSCs to maintain an oncogenic translational program required for relapse.
HostingRepository	PRIDE
AnnounceDate	2025-01-07
AnnouncementXML	Submission_2025-01-07_08:23:22.127.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-06 05:32:56	ID requested
⏵ 1	2025-01-07 08:23:22	announced

10.1016/J.CELREP.2024.115151;

submitter keyword: AML, GeLC-MS, chemotherapy

Simón Méndez-Ferre
contact affiliation	Cambridge Stem Cell Institute, Cambridge, United Kingdom, CB2 0AW
contact email	sm2116@cam.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058648
     1. Label: PRIDE project
     2. Name: Bone Marrow Mesenchymal Stromal Cells Support Translation in Refractory Acute Myeloid Leukemia