High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression of AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80 patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at various levels, but was undetectable in 35 patients (44%). AID PCR positivity was associated with unmutated IGV(H) gene status (22 of 25 patients; P = 0.002) and unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53; P = 0.040). Using a threshold level of 0.01-fold expression compared to Ramos control cells, even more significant associations were observed (P = 0.001 for IGV(H); P = 0.002 for cytogenetics). A correlation was observed between individual AID levels and the percentage of V-H homology (R = 0.41; P = 0.001). AID positivity predicted unmutated IGV(H) status with an odds ratio of 8.31 (P = 0.003) and poor risk cytogenetics with an odds ratio of 3.46 (P = 0.032). Significance was retained after adjustment for Binet or Rai stages. AID mRNA levels were stable over time. These data suggest a potential role of AID as a prognostic marker in B-CLL.