Abstract
Fanconi anemia is an inherited disease characterized by genomic instability, hypersensitivity to DNA cross-linking agents, bone marrow failure, short stature, skeletal abnormalities, and a high relative risk of myeloid leukemia and epithelial malignancies. The 21 Fanconi anemia genes encode proteins involved in multiple nuclear biochemical pathways that effect DNA interstrand crosslink repair. In the past, bone marrow failure was attributed solely to the failure of stem cells to repair DNA. Recently, non-canonical functions of many of the Fanconi anemia proteins have been described, including modulating responses to oxidative stress, viral infection, and inflammation as well as facilitating mitophagic responses and enhancing signals that promote stem cell function and survival. Some of these functions take place in non-nuclear sites and do not depend on the DNA damage response functions of the proteins. Dysfunctions of the canonical and non-canonical pathways that drive stem cell exhaustion and neoplastic clonal selection are reviewed, and the potential therapeutic importance of fully investigating the scope and interdependences of the canonical and non-canonical pathways is emphasized.
Funder
U.S. Department of Veterans Affairs
National Institutes of Health
Subject
General Pharmacology, Toxicology and Pharmaceutics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference167 articles.
1. Familiare infantile perniziosaartige anaemia (pernizioses blutbild und konstitution).;G Fanconi;Jahrb Kinderhilkd.,1927
2. Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia.;S Latt;Proc Natl Acad Sci U S A.,1975
3. Diagnosis of Fanconi anemia in patients with bone marrow failure.;F Pinto;Haematologica.,2009
4. Prenatal and postnatal diagnosis and carrier detection of Fanconi anemia by a cytogenetic method.;A Auerbach;Pediatrics.,1981
5. Fludarabine-based protocol for human umbilical cord blood transplantation in children with Fanconi anemia.;M Aker;J Pediatr Hematol Oncol.,1999
Cited by
48 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献