Publication

Differential redox-regulation and mitochondrial dynamics in normal and leukemic hematopoietic stem cells: A potential window for leukemia therapy

Mattes, K., Vellenga, E. & Schepers, H., Dec-2019, In : Critical Reviews in Oncology/Hematology. 144, 14 p., 102814.

Research output: Contribution to journalReview articleAcademicpeer-review

The prognosis for many patients with acute myeloid leukemia (AML) is poor, mainly due to disease relapse driven by leukemia stem cells (LSCs). Recent studies have highlighted the unique metabolic properties of LSCs, which might represent opportunities for LSC-selective targeting. LSCs characteristically have low levels of reactive oxygen species (ROS), which apparently result from a combination of low mitochondria] activity and high activity of ROS-removing pathways such as autophagy. Due to this low activity, LSCs are highly dependent on mitochondrial regulatory mechanisms. These include the anti-apoptotic protein BCL-2, which also has crucial roles in regulating the mitochondrial membrane potential, and proteins involved in mitophagy.

Here we review the different pathways that impact mitochondrial activity and redox-regulation, and highlight their relevance for the functionality of both HSCs and LSCs. Additionally, novel AML therapy strategies that are based on interference with those pathways, including the promising BCL-2 inhibitor Venetoclax, are summarized.

Original languageEnglish
Article number102814
Number of pages14
JournalCritical Reviews in Oncology/Hematology
Volume144
Early online date25-Sep-2019
Publication statusPublished - Dec-2019

    Keywords

  • HSC, LSC, Mitochondria, ROS, BCL-2, Autophagy, Venetoclax, ACUTE MYELOID-LEUKEMIA, SELF-RENEWAL, DNA-DAMAGE, METABOLIC-REGULATION, OXIDATIVE STRESS, BCL-2 INHIBITION, GLUTAMINE-METABOLISM, RESPIRATORY-CHAIN, ENERGY-METABOLISM, INITIATING CELLS

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