Expression of Activation-induced Cytidine Deaminase in Malignant Lymphomas Infiltrating the Bone Marrow

Abstract

Somatic hypermutation of immunoglobulin genes and class switch recombination are pivotal processes in the germinal center (GC) reaction and have been implicated in the development of malignant B-cell lymphoma. Both processes require the enzyme activation-induced cytidine deaminase (AID). Expression of AID is largely restricted to GC B cells and B cells that undergo class switch recombination outside the GC. AID is also expressed in many B-cell lymphomas. This study investigates the expression of AID of malignant lymphomas infiltrating the bone marrow. Bone marrow trephines (n=130) with infiltration of Hodgkin lymphoma and non-Hodgkin lymphoma of B cell and T-cell type and trephines with reactive lymphoid follicles (n=16) were analyzed immunohistochemically for AID protein. AID is expressed in bone marrow infiltrates of malignant lymphomas. AID was generally detected in lymphomas of GC origin. Tumor cells of hairy cell leukemia are mostly AID. There is apparently no different expression of AID found in bone marrow infiltrates of malignant lymphomas compared with a control group with nodal malignant lymphoma infiltrates (n=105). These results suggest that the expression pattern of AID in lymphoma infiltrates in the bone marrow reflects that of extramedullary lymphoma infiltrates.

In Vivo and In Vitro Studies Suggest a Possible Involvement of HPV Infection in the Early Stage of Breast Carcinogenesis via APOBEC3B Induction

“…Indeed, overexpression of other cytidine deaminases, APOBEC1 and activation-induced deaminase (AID) can cause hepatocellular carcinoma and T cell lymphomas in transgenic mice, respectively. Also, several other studies have disclosed expression of AID gene transcripts or proteins in gastric cancer [29] and human lymphoid malignancies [30], [31]. Very recently, A3B has been implicated by several groups independently as a source of mutations in various cancers including breast, bladder, lung, head and neck, and cervical cancers [25]–[28].…”

The prognostic importance of double-expressor subgroup and AID, UNG and mismatch repair protein expressions in diffuse large B-cell lymphomas

“…We have limited knowledge about the expression of UNG in DLBCL [9,[37][38][39][40][41][42]. The loss of UNG and mismatch repair proteins in murine patients have been shown to increase the rate of mutation and cause DLBCL-like disease, while only loss of UNG is shown to be protective [42].…”