biostudies-literatureLisi-Vega LECancer Research UKEuropean Commission Marie Sklodowska-Curie ActionsMPN Research FoundationBlood Cancer UKUK Research and InnovationSpain Ministry of Science and InnovationHorizon 2020 Framework ProgrammeMedical Research CouncilEuropean Hematology AssociationFondazione AIRC per la ricerca sul cancro ETSLeukemia & Lymphoma SocietyUK Research and Innovation Medical Research CouncilWellcome Trust115151https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617453biostudies-literatureUnknown44(1)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 (internal tandem duplication) and nucleophosmin (NPMc) mutations, protein synthesis levels increase in refractory AML dependent on nestin+ BMSCs. Inhibiting cap-dependent Cell reportsBone marrow mesenchymal stromal cells support translation in refractory acute myeloid leukemia.PMC7617453226795/Z/22/Z203151/Z/16/Z203151/A/16/ZC61367/A26670MC_PC_17230MR/V005421/1Mendez-Ferrer SForte DWilliams TLSerafini MPievani AGarcia-Fernandez MLisi-Vega LEfalseBone marrow mesenchymal stromal cells support translation in refractory acute myeloid leukemia.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 (internal tandem duplication) and nucleophosmin (NPMc) mutations, protein synthesis levels increase in refractory AML dependent on nestin+ BMSCs. Inhibiting cap-dependent 2025-01-01T00:00:00Z2025 Jan2026-06-01T14:47:15.856Z2025-04-04T02:04:48.778ZS-EPMC76174533993219010.1016/j.celrep.2024.115151