Table 3 Studies revealing the association between altered ROS levels and damaged hematopoiesis

↑ ROS: augments genomic instability

Excessive iron in MDS patients renders ROS accumulation and then augments genomic instability of the pre-leukemic clone, which accelerates transformation to AML

Pullarkat et al. [280]

↑ ROS: oxidative stress, triggering early hematopoietic cell apoptosis

In an IOL mouse model, leukemic blasts infiltrated the liver and spleen, with fibrosis, extensive necrosis of BM, and massive blast accumulation. Meanwhile, iron is mutagenic and thereby promotes clonal evolution in MDS through DNA damage

Chan et al. [281]

↑ ROS: activation of ROS-related signaling pathway

Heightened ROS levels regulating the expression of redox-sensitive transcription factors (e.g., Nrf2, NF-κB, and HIF1) to prompt leukemogenesis

Zhou et al. [282]

↑ ROS: oxidative stress, DNA double-strand breaks, cell cycle retardation

Based on an MDS murine model, increased ROS levels and mutation frequency in NHD13 BMNCs were observed. In parallel, DNA impairment and oncogenic mutations caused by oxidative stress can expedite the transformation of MDS to AML

Chung et al. [283]

↑ ROS: reduces the ratio and clonogenic function of HSPCs

IOL enhances ROS levels through NOX4 and p38MAPK signaling, thereby affecting the hematopoiesis of BM and the engraftment of HSCs

Chai et al. [207]

↑ ROS: mitochondrial fragmentation and enhanced autophagy in MSCs

IOL contributed to high ROS levels, lowered cell viability and ATP concentrations, mitochondrial fragmentation, and autophagy in MSCs. ICT or antioxidants could deteriorate the change

Zheng et al. [284]

↑ ROS: retards the growth of immature hematopoietic cells

Ferrous ammonium sulfate mediated immature hematopoietic cells’ growth retardation and apoptosis by ROS activation of p38MAPK and JNK pathways, which had negative effects on hematopoiesis

Tanaka et al. [285]

↓ ROS: maintains the self-renewal and multilineage differentiation potential of human HSCs

The small-molecule antioxidant chrysin is able to inhibit ROS-activated apoptosis, and maintain multipotency and long-term activity of hematopoietic stem/progenitor cells

Li et al. [286]

↓ ROS: suppression of apoptosis of hematopoietic stem/progenitor cells

Alpha-lipoic acid can promote HPSC development by upregulating HIF1α in response to a hypoxic environment, also decreasing ROS levels to inhibit HPSC apoptosis

Dong et al. [287]

↑ ROS: inhibits the reconstitution potential of HSPCs

Ionizing radiation caused the rapid and transient increase of ROS and then p38MAPK pathway activation that affects the self-renewal potential of human HSCs

Henry et al. [288]

↑ ROS: retards the proliferation and differentiation of MSCs

IOL results in elevated ROS production and activates Wnt/β-catenin signaling to engage in MDS progression

Huang et al. [206]

↑ ROS: lower membrane potential and DNA damage of SdhcV69E-derived HSCs

Mitochondrial complex II dysfunctions or replicative stresses contribute to white blood cell count decrease, macrocytic anemia, thrombocytosis, as well as ROS accumulation and DNA impairment of HSCs

Harada et al. [289]