Fig. 1: ROS exert selective pressure for the clonal evolution in AML.

Different from HSC, which mainly obtains energy through glycolysis, LSC mainly relies on oxidative phosphorylation (OXPHOS) to support cell metabolism and survival, thus producing a relatively high ROS level [94]. Chemotherapeutic drugs and chronic inflammation also promote ROS production [37, 41, 42]. In addition, oncogenes such as FLT3(ITD) and BCR-ABL1 can also facilitate intracellular ROS production through NOX or RAC2-MRC cIII pathway [95, 96]. High levels of ROS not only lead to mutagenic reactions in the DNA, but also inhibit DNA repair enzymes, resulting in genomic instability, which may be an important driver of LSC evolution [97]. Rac Rac GTPase; TCA tricarboxylic acid; MRC-cIII mitochondrial respiratory chain complex III.