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dc.contributor.authorHeydt, Q.
dc.contributor.authorXintaropoulou, C.
dc.contributor.authorClear, A.
dc.contributor.authorAustin, M.
dc.contributor.authorPislariu, I.
dc.contributor.authorMiraki-Moud, F.
dc.contributor.authorCutillas, P.
dc.contributor.authorKorfi, K.
dc.contributor.authorCalaminici, M.
dc.contributor.authorCawthorn, W.
dc.contributor.authorSuchacki, K.
dc.contributor.authorNagano, A.
dc.contributor.authorGribben, J. G.
dc.contributor.authorSmith, M.
dc.contributor.authorCavenagh, J. D.
dc.contributor.authorOakervee, H.
dc.contributor.authorCastleton, Anna
dc.contributor.authorTaussig, D.
dc.contributor.authorPeck, B.
dc.contributor.authorWilczynska, A.
dc.contributor.authorMcNaughton, L.
dc.contributor.authorBonnet, D.
dc.contributor.authorMardakheh, F.
dc.contributor.authorPatel, B.
dc.date.accessioned2021-09-30T11:56:04Z
dc.date.available2021-09-30T11:56:04Z
dc.date.issued2021en
dc.identifier.citationHeydt Q, Xintaropoulou C, Clear A, Austin M, Pislariu I, Miraki-Moud F, et al. Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence. Nat Commun. 2021 Sep 17;12(1).en
dc.identifier.pmid34535653en
dc.identifier.doi10.1038/s41467-021-25540-4en
dc.identifier.urihttp://hdl.handle.net/10541/624609
dc.description.abstractThe specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41467-021-25540-4en
dc.titleAdipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistenceen
dc.typeArticleen
dc.contributor.departmentCentre for Haemato-Oncology, Barts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, UKen
dc.identifier.journalNature Communicationsen
dc.description.noteen]
refterms.dateFOA2021-10-13T08:30:44Z


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