Fig. 1

The different mechanisms of ROS generation in leukemia cells and their role in leukemogenesis. (1) MtDNA mutations lead to alternations in the mtETC, resulting in increased ROS production promoting DNA damage, genomic instability, and drug resistance in AML. (2) Activated genetic polymorphisms of CYP450 in AML, ALL, and CLL, generate high ROS levels contributing to cell proliferation, survival, drug resistance, and disease relapse. (3) Elevated XO/XDH activity leads to increased ROS & OS attributed to AML relapse and progression. (4) Leukemic oncogene activity (BCR/ABL, Flt3-ITD, Ras, c-Kit, JAK2 V617F) induce NADPH elevation and increased NOX activity resulting in elevated ROS levels which promote DNA damage, genetic instability, proliferation, survival, migration, and drug resistance in leukemic cells. (5) Increased ROS generated from leukemic cells, oncogene mutations, abnormal metabolism with an ineffective antioxidant system results in increased OS which aberrantly expresses Jab1/COPS5 leading to AML proliferation, progression, and relapse. Abbreviations: mitochondrial ETC, electron transport chain; CYP450, cytochrome P450; XO, xanthine oxidase; XDH, xanthine dehydrogenase; AML, acute myeloid leukemia; BCR/ABL, Breakpoint cluster region-Abelson leukemia virus; Flt3-FTD, FMS-like tyrosine kinase 3-internal tandem duplication; c-Kit, receptor tyrosine kinase; JAK2 V617F, Janus kinase 2 V617F; Jab1/COPS5, c-Jun activation domain-binding protein-1