Activation-induced cytidine deaminase displays an alternative co-factor for modulating PIM1 expression in diffuse...

Diffuse large B cell lymphoma (DLBCL) is a B cell neoplasm characterized by high PIM1 expression, which is responsible for poor prognosis. Activation-induced cytidine deaminase (AID) is closely linked to PIM1 hypermutation in DLBCL. Here, we found that the DNA methyltransferase 1 (DNMT1) level decreased with AID depletion in the DLBCL cell line SU-DHL-4, and increased significantly when AID was highly expressed. The double ablation of AID and DNMT1 contributed to increased PIM1 expression, which initiated faster DLBCL cell proliferation, whereas ten-eleven translocation family member 2 (TET2) decreased with AID deficiency and increased with AID overexpression in DLBCL cell line OCI-LY7. The double depletion of AID and TET2 was associated with decreased PIM1 levels and showed slower cell division. We suggest an alternative role of AID as a co-factor of DNA methylation cooperated with DNMT1, or of DNA demethylation associated with TET2 in modulating PIM1 expression. Our findings demonstrate that AID interacts with either DNMT1 or TET2 to form a complex to bind with a PIM1 promoter and thus is responsible for the modulation of PIM1 expression. These results provide insights into an alternative role of AID to DLBCL-associated genes.