Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, Canada.
Terry Fox Laboratory, BC Cancer Research Centre, University of British Columbia, Vancouver, Canada.
Leuk Lymphoma. 2021 Oct;62(10):2331-2341. doi: 10.1080/10428194.2021.1910685. Epub 2021 Jun 1.
There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. We also review the role of oxidative phosphorylation (OxPhos) in maintaining leukemia stem cells (LSCs), how recurrent genomic alterations in AML alter downstream metabolism, and focus on how the BCL-2 pathway and the mitochondria are inextricably linked in AML. Thus, we provide an overview of the mitochondria and metabolism in the context of our new therapeutic world for AML and outline how targeting these vulnerabilities may produce novel therapeutic strategies.
关于代谢和线粒体在急性髓系白血病（AML）中的作用，相关知识呈爆炸式增长。我们最近还看到了几波新的疗法改变了 AML 的治疗格局，例如选择性 B 细胞淋巴瘤 2（BCL-2）抑制剂 venetoclax。在这种新背景下，我们综述了代谢和线粒体在 AML 发病机制中的作用的快速发展的文献，以及这些机制如何与 AML 新型治疗药物的作用机制交织在一起。我们还综述了氧化磷酸化（OxPhos）在维持白血病干细胞（LSCs）中的作用、AML 中反复出现的基因组改变如何改变下游代谢，以及重点关注 BCL-2 通路和线粒体在 AML 中是如何紧密相连的。因此，我们概述了 AML 新治疗领域中与线粒体和代谢有关的内容，并阐述了靶向这些脆弱性可能产生新的治疗策略。
