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Leukemia and chromosomal instability in aged Fancc-/- mice
Donna Cerabona1, Zejin Sun2, Grzegorz Nalepa3
1Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN.
Experimental Hematology
|February 11, 2016
Summary
Aging mice lacking Fanconi anemia complementation group C (Fancc) develop leukemia. This study establishes a new preclinical model for Fanconi anemia-associated cancers.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Fanconi anemia (FA) is an inherited genomic instability disorder.
- FA is linked to a high risk of myelodysplasia and acute myeloid leukemia (AML).
- Young FA mice do not develop cancer, limiting preclinical research on malignant hematopoiesis.
Purpose of the Study:
- To establish a preclinical model for Fanconi anemia-associated leukemogenesis.
- To investigate the role of aging in the development of hematologic neoplasms in FA.
Main Methods:
- Aging analysis of Fancc-deficient (Fancc-/-) mice.
- Assessment of hematopoietic chromosomal instability and aneuploidy.
- Monitoring for the development of hematologic neoplasms.
Main Results:
- Aging Fancc-/- mice are prone to developing genomically unstable AML and other hematologic neoplasms.
- Aneuploidy precedes malignant transformation in Fancc-/- hematopoiesis.
- Fancc-/- mice exhibit age-dependent hematopoietic chromosomal instability and leukemia development.
Conclusions:
- Aging Fancc-/- mice recapitulate the clinical phenotype of human FA.
- This model provides a proof of concept for studying FA-associated leukemogenesis.
- The findings highlight the importance of age in FA cancer development.
