Fanconi anemia and leukemia: tracking the genes

A review of all of the cases of Fanconi anemia (FA) reported to the International Fanconi Anemia Registry (IFAR) indicates that at least 15% manifest acute myelogenous leukemia (AML) or preleukemia. These patients usually have karyotypically abnormal bone marrow clones, but do not exhibit chromosomal translocations involving breakpoints associated with specific oncogenes; leukemia in FA is more likely to be a multi-step process than a single step transformation. The cellular defect in FA results in chromosomal instability, hypersensitivity to DNA damage, and hypermutability for allele-loss mutations. An update of current research to identify the molecular defect in FA is presented. Characterization of the FA genes should further our understanding of the etiology of leukemia.