Origin and features of the 2 subsets of chronic lymphocytic leukemia. The development of unmutated CLL (U-CLL) is likely to be from a naive B cell that has encountered antigen but with insufficient stimulus to form a germinal center (GC). This subset has a poorer prognosis, displays a preference for V_1-69 genes, and frequently expresses ZAP-70 and activation-induced cytidine deaminase (AID). In contrast, mutated CLL (M-CLL) develops from a cell that, following antigen encounter, has undergone somatic mutation and presumably antigen selection in the GC. The final neoplastic event is likely to have occurred after exit from the GC. This subset has a superior prognosis and displays a preference for V_4-34 genes, but infrequently expresses ZAP-70 or AICD.