title: Leukemia and chromosomal instability in aged Fancc-/- mice.
abstract: Fanconi anemia (FA) is an inherited disorder of genomic instability associated with high risk of myelodysplasia and acute myeloid leukemia (AML). Young mice deficient in FA core complex genes do not naturally develop cancer, hampering preclinical studies on malignant hematopoiesis in FA. Here we describe that aging Fancc(-/-) mice are prone to genomically unstable AML and other hematologic neoplasms. We report that aneuploidy precedes malignant transformation during Fancc(-/-) hematopoiesis. Our observations reveal that Fancc(-/-) mice develop hematopoietic chromosomal instability followed by leukemia in an age-dependent manner, recapitulating the clinical phenotype of human FA and providing a proof of concept for future development of preclinical models of FA-associated leukemogenesis.
authors: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
authors: Donna
authors: D
authors: Cerabona
authors: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
authors: Zejin
authors: Z
authors: Sun
authors: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN; Division of Pediatric Hematology-Oncology, Riley Hospital for Children, Indianapolis, IN. Electronic address: gnalepa@iu.edu.
authors: Grzegorz
authors: G
authors: Nalepa
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D000375:Aging / Q000235:genetics*; D000782:Aneuploidy; D000818:Animals; D043171:Chromosomal Instability; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D052218:Fanconi Anemia Complementation Group C Protein / Q000172:deficiency / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C497652:Fancc protein, mouse; D052218:Fanconi Anemia Complementation Group C Protein