Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy
Abstract
Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin + BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo . Unlike bulk stroma, nestin + BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated hematopoietic stem cells (HSCs). Nestin + cell depletion delays leukemogenesis in primary AML mice and selectively decreases AML, but not normal, cells in chimeric mice. Nestin + BMSCs support survival and chemotherapy relapse of AML through increased oxidative phosphorylation, tricarboxylic acid (TCA) cycle activity, and glutathione (GSH)-mediated antioxidant defense. Therefore, AML cells co-opt energy sources and antioxidant defense mechanisms from BMSCs to survive chemotherapy.
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BibTeX
@article{forte2026bone,
title = {{Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy}},
author = {Dorian Forte and María García-Fernández and Abel Sánchez-Aguilera and Vaia Stavropoulou and Claire Fielding and Daniel Martín-Pérez and Juan Antonio López and Ana S.H. Costa and Laura Tronci and Efterpi Nikitopoulou and Michael Barber and Paolo Gallipoli and Ludovica Marando and Carlos López Fernández de Castillejo and Alexandar Tzankov and Sabine Dietmann and Michele Cavo and Lucia Catani and Antonio Curti and Jesús Vázquez and Christian Frezza and Brian Huntly and Juerg Schwaller and Simón Méndez-Ferrer},
journal = {Cell Metabolism},
year = {2026},
month = oct,
doi = {10.1016/j.cmet.2020.09.001},
url = {https://hal.science/hal-05787336v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy
AU - Dorian Forte
AU - María García-Fernández
AU - Abel Sánchez-Aguilera
AU - Vaia Stavropoulou
AU - Claire Fielding
AU - Daniel Martín-Pérez
AU - Juan Antonio López
AU - Ana S.H. Costa
AU - Laura Tronci
AU - Efterpi Nikitopoulou
AU - Michael Barber
AU - Paolo Gallipoli
AU - Ludovica Marando
AU - Carlos López Fernández de Castillejo
AU - Alexandar Tzankov
AU - Sabine Dietmann
AU - Michele Cavo
AU - Lucia Catani
AU - Antonio Curti
AU - Jesús Vázquez
AU - Christian Frezza
AU - Brian Huntly
AU - Juerg Schwaller
AU - Simón Méndez-Ferrer
PY - 2026
DA - 2026/10/08
JO - Cell Metabolism
DO - 10.1016/j.cmet.2020.09.001
UR - https://hal.science/hal-05787336v1
AB - Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin + BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo . Unlike bulk stroma, nestin + BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated hematopoietic stem cells (HSCs). Nestin + cell depletion delays leukemogenesis in primary AML mice and selectively decreases AML, but not normal, cells in chimeric mice. Nestin + BMSCs support survival and chemotherapy relapse of AML through increased oxidative phosphorylation, tricarboxylic acid (TCA) cycle activity, and glutathione (GSH)-mediated antioxidant defense. Therefore, AML cells co-opt energy sources and antioxidant defense mechanisms from BMSCs to survive chemotherapy.
SN - 1550-4131
ER -