Expression of activation-induced cytidine deaminase is associated with a poor prognosis of diffuse large B cell lymphoma patients treated with CHOP-based chemotherapy

AbstractWe assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (37%), and aberrant SHM in PAX5, RhoH/TTF, and/or MYC in 7 PCLBCLs (54%), leg type, and 10 PCFCL patients (53%). The majority of mutations consisted of single base-pair substitutions (n = 54) with rare deletions/insertions (n = 4), and displayed molecular features typical of the SHM process. Quantitative real-time PCR and immunohistochemical stainings for activation-induced cytidine deaminase, which is indispensable for SHM, demonstrated significantly higher expression in PCLBCL, leg type. Our results suggest that (aberrant) SHM may contribute to the pathogenesis of PCLBCL, leg type, and PCFCL and is not restricted to diffuse large B-cell lymphomas with an aggressive clinical behavior.

Download Full-text

Activation-Induced Cytidine Deaminase Expression in Diffuse Large B-Cell Lymphoma With a Paracortical Growth Pattern: A Lymphoma of Possible Interfollicular Large B-Cell Origin

Archives of Pathology & Laboratory Medicine ◽

10.5858/134.3.449 ◽

2010 ◽

Vol 134 (3) ◽

pp. 449-456

Author(s):

Nadine S. Aguilera ◽

Aaron Auerbach ◽

Carol L. Barekman ◽

Jack Lichy ◽

Susan L. Abbondanzo

Keyword(s):

B Cells ◽

B Cell ◽

Heavy Chain ◽

Cell Lymphoma ◽

Cytidine Deaminase ◽

B Cell Lymphoma ◽

Immunoglobulin Heavy Chain ◽

Large B Cell Lymphoma ◽

Activation Induced Cytidine Deaminase ◽

Large B Cell

Abstract Context.—Activation-induced cytidine deaminase, necessary for immunoglobulin somatic hypermutation and class switch recombination, is usually expressed within the follicular dendritic network but is also expressed in a population of interfollicular large B cells outside the germinal center. Objective.—To report 7 cases of diffuse large B-cell lymphoma with a distinct paracortical distribution. Expression of activation-induced cytidine deaminase, previously described in interfollicular large B cells, was evaluated. Design.—A panel of immunohistochemical markers, including double staining for activation-induced cytidine deaminase and CD20, was used to illustrate the cases. Molecular studies were performed by polymerase chain reaction in the paraffin-embedded tissue for t(14;18) chromosomal translocation and immunoglobulin heavy chain and T-cell receptor rearrangements. Results.—Patients included 3 males and 4 females ranging in age from 11 to 59 years (mean, 39 years). All specimens were lymph nodes (4 from the groin, 2 from the neck, and 1 from the axilla). Malignant lymphocytes were positive for CD20 and negative for CD5 and CD10. Staining for CD30, CD43, and BCL-2 was variable. The malignant cells showed at least focal staining with activation-induced cytidine deaminase. All cases were found to be monoclonal by immunoglobulin heavy-chain gene rearrangement or showed light-chain restriction. None of the tested cases showed t(14;18). Conclusions.—Diffuse large B-cell lymphoma with a paracortical distribution is unusual and may be a distinct morphologic variant. More study is necessary to determine the stage of B-cell development and the cell of origin of these tumors. However, activation-induced cytidine deaminase expression suggests they may arise from a putative interfollicular large B cell.

Download Full-text

Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients

Journal of Clinical Medicine ◽

10.3390/jcm10081768 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1768

Author(s):

Zhitao Wang ◽

Rui Jiang ◽

Qian Li ◽

Huiping Wang ◽

Qianshan Tao ◽

...

Keyword(s):

B Cell ◽

Poor Prognosis ◽

Cell Lymphoma ◽

Suppressor Cells ◽

B Cell Lymphoma ◽

Pathological Process ◽

Newly Diagnosed ◽

Large B Cell Lymphoma ◽

Accumulation Mechanism ◽

Large B Cell

Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients.

Download Full-text