Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 09 2021
17 09 2021
Historique:
received:
03
09
2020
accepted:
17
08
2021
entrez:
18
9
2021
pubmed:
19
9
2021
medline:
13
10
2021
Statut:
epublish
Résumé
The 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.
Identifiants
pubmed: 34535653
doi: 10.1038/s41467-021-25540-4
pii: 10.1038/s41467-021-25540-4
pmc: PMC8448863
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5507Subventions
Organisme : Medical Research Council
ID : MR/M021394/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : CRUK A21019
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C16420/A18066
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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