The dark side of activation-induced cytidine deaminase: Relationship with leukemia and beyond

Activation-induced cytidine deaminase (AID) is a unique cellular enzyme that can trigger point mutations and chromosomal translocations, both of which potentially disturb normal cellular metabolism and affect cancer initiation and progression. The involvement of AID in the progression of leukemia has been suggested by multiple groups on the basis of observations of the statistical correlation between AID expression and a poor prognosis of B-cell chronic lymphocytic leukemia. The fact that ectopic expression of AID in mice results in tumors of the lung and T-lymphocytes suggests an oncogenic role for AID. The inducible nature of AID expression indicates that AID might be induced and cause oncogenic mutations, even in epithelial tissues, where AID expression is absent or very weak under normal conditions. If AID can be induced in epithelial cells by inflammatory signals, as from B-lymphocytes, it may be involved in various pathologic conditions, including inflammation- and infection-associated cancers, for which the molecular mechanism is largely unknown, despite the clinical significance of these diseases.