Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.

Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy. Cell Metab. 2020 Sep 16;: Authors: Forte D, García-Fernández M, Sánchez-Aguilera A, Stavropoulou V, Fielding C, Martín-Pérez D, López JA, Costa ASH, Tronci L, Nikitopoulou E, Barber M, Gallipoli P, Marando L, Fernández de Castillejo CL, Tzankov A, Dietmann S, Cavo M, Catani L, Curti A, Vázquez J, Frezza C, Huntly BJ, Schwaller J, Méndez-Ferrer S 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 ...
Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab Source Type: research