title: Oxidative stress in Fanconi anemia hematopoiesis and disease progression.
abstract: Patients with the genomic instability syndrome Fanconi anemia (FA) commonly develop progressive bone marrow failure and have a high risk of cancer. The prominent role of the FA protein family involves DNA damage response and/or repair. Oxidative stress, defined as an imbalance between the production of reactive oxygen species and antioxidant defense, is considered to be an important pathogenic factor in leukemia-prone bone marrow diseases such as FA. Cellular responses inducing resistance to oxidative stress are important for cellular survival, organism lifespan, and cancer prevention, but until recently, mammalian factors regulating resistance to oxidative stress have not been well characterized. Significant evidence supports excessive apoptosis of hematopoietic stem/progenitor cells, induced by stresses, most significantly oxidative stress, as a critical factor in the pathogenesis of bone marrow failure and leukemia progression in FA. In this brief review, we discuss the functional link between FA proteins and oxidative DNA damage response/repair, with emphasis on the implication of oxidative stress in the pathophysiology and abnormal hematopoiesis in FA.
authors.affiliation: Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. wei.du@cchmc.org
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Adam
authors.forename: Reena
authors.initials: R
authors.lastname: Rani
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Qishen
authors.initials: Q
authors.lastname: Pang
mesh_terms: D000818:Animals; D018450:Disease Progression; D005199:Fanconi Anemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D051856:Fanconi Anemia Complementation Group Proteins / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000503:physiopathology; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D051856:Fanconi Anemia Complementation Group Proteins