Fanconi anemia (FA) consists of a group of at least five autosomal recessive 
disorders that share both clinical (e.g., birth defects and hematopoietic 
failure) and cellular (e.g., sensitivity to cross-linking agents and 
predisposition to apoptosis) features with each other. However, a common 
pathogenetic link among these groups has not been established. To identify 
genetic pathways that are altered in FA and characterize shared molecular 
defects, we used mRNA differential display to isolate genes that have altered 
expression patterns in FA cells. Here, we report that the expression of an 
interferon-inducible gene, MxA, is highly upregulated in cells of FA 
complementation groups A, B, C, and D, but it is suppressed in FA group C cells 
complemented with wild-type FAC cDNA as well as in non-FA cells. A 
posttranscriptional mechanism rather than transcriptional induction appears to 
account for MxA overexpression. Forced expression of MxA in Hep3B cells enhances 
their sensitivity to mitomycin C and induces apoptosis, similar to the FA 
phenotype. Thus, MxA is a downstream target of FAC and is the first genetic 
marker to be identified among multiple FA complementation groups. These data 
suggest that FA subtypes converge onto a final common pathway, which is 
intimately related to the interferon signaling mechanism. Constitutive activity 
of this pathway may explain a number of the phenotypic features of FA, 
particularly the pathogenesis of bone marrow failure.