Abstract
Fanconi anemia （ FA） is a rare autosomal recessive disorder of hematopoiesis, characterized by chromosome instability. FA patients are susceptible to hematopoietic neoplasms such as acute myeloid leukemia and various types of epithelial malignancies. The disease is classified into more than 10 genetically different groups, and 8 FA genes have been identified. These gene products function in a common pathway, in which FANCD2, a downstream component, in collaboration with BRCA1, regulates DNA damage response. Notably, FANCD1 has been proved to be identical with BRCA2. These findings have led to a proposal of the FA/BRCA pathway. FANCD2 also controls the cell cycle checkpoint, by interacting with ATM and NBS1. Fancd2-null mice show an increased incidence of various types of epithelial malignancies. Emerging evidence suggests that the acquired inactivation of FA genes is involved in carcinogenesis/tumor progression and tumor sensitivity to chemotherapeutic DNA crosslinkers.
