Activation-induced cytidine deaminase overexpression in double-hit lymphoma: potential target for novel anticancer therapy

Jingcheng Zhang,Mingzhe Zhao,Huixian Hu,Yifen Shi,He Huang

doi:10.1038/s41598-020-71058-y

Abstract

Activation-induced cytidine deaminase (AID) is one kind of the mutant enzymes, which target regulating the immunoglobulin (Ig) gene in Burkitt’s lymphoma to initiate class switch recombination (CSR), resulting in c-Myc chromosomal translocation. However, it is not clear that whether AID induces c-Myc/IgH translocation in double-hit lymphoma (DHL) with c-Myc gene translocation. In this study, the AID in DHL tissues and classical diffuse large b-cell lymphoma (DLBCL) tissues were compared. The results suggested that AID is of important value in predicting DHL, stronger CSR of AID was observed in DHL patients, which exhibited AID overexpression and c-Myc gene translocation of DHL after CSR induction. It is concluded that AID directly induces CSR in DHL and may result in c-Myc gene translocation. Targeting AID may be a good treatment regimen for DHL.

Highlights

Activation-induced cytidine deaminase (AID) is one kind of the mutant enzymes, which target regulating the immunoglobulin (Ig) gene in Burkitt’s lymphoma to initiate class switch recombination (CSR), resulting in c-Myc chromosomal translocation
double-hit lymphoma (DHL) is more common in GCB immunophenotype, and Ki-67 is higher than diffuse large b-cell lymphoma (DLBCL) (Table 1)
We followed up the patients for 2 years, and the AID-positive DHL was worse than the AID-positive DLBCL OS, with a statistical difference (P = 0.025), (Fig. 1D), but there is no difference between AID-negative DHL and DLBCL (Fig. 1E)

Summary

Introduction

Activation-induced cytidine deaminase (AID) is one kind of the mutant enzymes, which target regulating the immunoglobulin (Ig) gene in Burkitt’s lymphoma to initiate class switch recombination (CSR), resulting in c-Myc chromosomal translocation. The AID in DHL tissues and classical diffuse large b-cell lymphoma (DLBCL) tissues were compared. It is concluded that AID directly induces CSR in DHL and may result in c-Myc gene translocation. Activation-induced cytidine deaminase (AID) in the germinal center induce the high mutation degree of B cells, which produce different-encoded antibody B cells to complete CSR, leading to the occurrence of proto-cancerous chromosomal translocation between immunoglobulin c-Myc and IgH in B c ells[6,7]. Immunohistochemistry and Western Blot were used to detect and analyze the AID expression in 20 DHL and 20 classic DLBCL tissues respectively. The results of this study will provide reference for clinical diagnosis, prognosis and molecular targeted therapy of DHL

Methods

Results

Conclusion