英国剑桥大学干细胞研究所Simón Méndez-Ferrer、瑞士巴塞尔大学Juerg Schwaller等研究人员合作发现，骨髓间充质干细胞支持急性髓样白血病生物能并增强抗氧化防御能力，从而逃逸化疗。2020年9月22日《细胞—代谢》杂志在线发表了这项成果。

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

Author: Dorian Forte, María García-Fernández, Abel Sánchez-Aguilera, Vaia Stavropoulou, Claire Fielding, Daniel Martín-Pérez, Juan Antonio López, Ana S.H. Costa, Laura Tronci, Efterpi Nikitopoulou, Michael Barber, Paolo Gallipoli, Ludovica Marando, Carlos López Fernández de Castillejo, Alexandar Tzankov, Sabine Dietmann, Michele Cavo, Lucia Catani, Antonio Curti, Jesús Vázquez, Christian Frezza, Brian J. Huntly, Juerg Schwaller, Simón Méndez-Ferrer

Issue&Volume: 2020-09-22

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.

DOI: 10.1016/j.cmet.2020.09.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30479-4